Imidazolyl-cyclic acetals

ABSTRACT

Compounds of the following backbone structure: 
                 
 
which are useful as Tumor necrosis factor (TNF) inhibitors in treating disease related to elevated TNF.

This application is a divisional application of U.S. application Ser. No. 09/456,360, filed Dec. 8, 1999 now U.S. Pat. No. 6,602,877 which is a continuation application of International Application No. PCT/GB98/01711, filed Jun. 12, 1998, which is entitled to the benefit of U.S. Provisional Application No. 60/052,185, filed Jul. 10, 1997 and U.S. Provisional Application No. 60/085,499, filed May 14, 1998, and which claims priority to GB 9712270.0, filed Jun. 12, 1997, and GB 9724678.9, filed Nov. 21, 1997.

This invention is directed to imidazolyl-cyclic acetals, their preparation, pharmaceutical compositions containing these compounds, and their pharmaceutical use in the treatment of disease states capable of being modulated by the inhibition of TNF.

Tumour necrosis factor (TNF) is an important pro-inflammatory cytokine which causes hemorrhagic necrosis of tumors and possesses other important biological activities. TNF is released by activated macrophages, activated T-lymphocytes, natural killer cells, mast cells and basophils, fibroblasts, endothelial cells and brain astrocytes among other cells.

The principal in vivo actions of TNF can be broadly classified as inflammatory and catabolic. It has been implicated as a mediator of endotoxic shock, inflammation of joints and of the airways, immune deficiency states, allograft rejection, and in the cachexia associated with malignant disease and some parasitic infections. In view of the association of high serum levels of TNF with poor prognosis in sepsis, graft versus host disease and adult respiratory distress syndrome, and its role in many other immunologic processes, this factor is regarded as an important mediator of general inflammation.

TNF primes or activates neutrophils, eosinophils, and endothelial cells to release tissue damaging mediators and increase the expression of adhesion molecules. In fibroblasts, TNF stimulates the production of collagenase, an enzyme implicated in joint destruction in rheumatoid arthritis. TNF also activates monocytes, macrophages and T-lymphocytes to cause the production of colony stimulating factors and other pro-inflammatory cytokines such IL-1, IL-6, IL-8 and GM-CSF, which in some cases mediate the end effects of TNF. The ability of TNF to activate T-lymphocytes, monocytes, macrophages and related cells has been implicated in the progression of Human Immunodeficiency Virus (HIV) infection. In order for these cells to become infected with HIV and for HIV replication to take place the cells must be maintained in an activated state. Cytokines such as TNF have been shown to activate HIV replication in monocytes and macrophages. Features of endotoxic shock such as fever, metabolic acidosis, hypotension and intravascular coagulation are thought to be mediated through the actions of TNF. The cachexia associated with certain disease states is mediated through indirect effects on protein catabolism. TNF also promotes bone resorption and acute phase protein synthesis.

TNF-alpha inhibits surfactant protein C gene transcription, which may contribute to abnormalities of surfactant homeostasis associated with pulmonary injury and infection, induces mucin hypersecretion and mediates the recruitment of neutrophils and eosinophils during airway inflammation. Although TNF-alpha inhibits collagen synthesis in fibroblasts, a number of studies point to it being pro-fibrotic in vivo. Thus, by inhibiting TNF-alpha production, the compounds of the invention have potential in suppressing the inflammation and airways remodelling that occurs in asthma.

TNF-alpha inhibits the ability of insulin to stimulate glucose uptake in adipose tissue. In obesity the overproduction of TNF is thought to cause an insulin-resistant state. Thus, by blocking TNF release the compounds of the invention have anti-diabetic potential.

TNF-alpha can induce angiogenesis in normally avascular tissue, possibly through upregulation of other pro-inflammatory cytokines, upregulation of adhesion molecules, stimulation of matrix mettalloproteinase expression and increased prostaglandin production. Thus, inhibition of TNF-alpha release by compounds of the invention will have benefit in angiogenesis dependent diseases including arthritis, diabetic retinopathies and ischemia induced diseases (myocardial infarction) and cancer.

The discussion herein relates to disease states associated with TNF including those disease states related to the production of TNF itself, and disease states associated with other cytokines, such as, but not limited to IL-1 or IL-6, that are modulated by association with TNF. For example, a IL-1 associated disease state, where IL-1 production or action is exacerbated or secreted in response to TNF, would therefore be considered a disease state associated with TNF. TNF-alpha and TNF-beta are also herein referred to collectively as “TNF” unless specifically delineated otherwise, since there is a close structural homology between TNF-alpha (cachectin) and TNF-beta (lymphotoxin) and each of them has a capacity to induce similar biological responses and bind to the same cellular receptor.

We have now found a novel group of imidazolyl-cyclic acetals which have valuable pharmaceutical properties, in particular the ability to regulate proteins that mediate cellular activity, for example TNF.

Thus, in one aspect, the present invention is directed to compounds of general formula (I):

wherein:

-   -   R¹ is optionally substituted heteroaryl;     -   R² is optionally substituted aryl or optionally substituted         heteroaryl;     -   R³ represents a group —L¹—R⁷ or —L²—R⁸         [where L¹ represents a straight- or branched-chain alkylene         linkage containing from 1 to about 6 carbon atoms optionally         substituted by halogen or oxo; R⁷ is hydrogen, aryl, cyano,         cycloalkyl, heteroaryl, heterocycloalkyl, nitro, —S(O)_(n)R⁹,         (where R⁹ is alkyl, aryl, arylalkyl, cycloalkyl, heteroaryl,         heteroarylalkyl, or heterocycloalkyl and n is zero or an integer         1 or 2), —NHSO₂R⁹, —C(═Z)OR¹⁰ (where Z is an oxygen or sulphur         atom and R¹⁰ is hydrogen or R⁹), —C(═Z)R¹⁰, —OR¹⁰,         —N(R¹¹)—C(═Z)R⁹ (where R¹¹ is hydrogen or alkyl), —NY¹Y² {where         Y¹ and Y² are independently hydrogen, alkenyl, alkyl, alkynyl,         aryl, arylalkyl, cycloalkenyl, cycloalkyl, heteroaryl or         heteroarylalkyl, or the group —NY¹Y² may form a 5-7 membered         cyclic amine which may optionally contain a further heteroatom         selected from O, S, or NY³ (where Y³ is hydrogen, alkyl, aryl,         arylalkyl, —CHO, —C(═Z)R⁹ or —SO₂R⁹), or which may also be fused         to additional aryl, heteroaryl, heterocycloalkyl or cycloalkyl         rings to form a bicyclic or tricyclic ring system}, —SO₂—NY¹Y²,         —C(═Z)—NY¹Y², —N(R¹¹)—C(═Z)—NY¹Y², —N(OR¹⁰)—C(═Z)—NY¹Y²,         —N(OR¹⁰)—C(═Z)R¹⁰, —C(═NOR¹⁰)R¹⁰, —C(═Z)NR¹⁰OR¹² (where R¹² is         hydrogen, alkyl, aryl or arylalkyl), —N(R¹¹)—C(═NR¹³)—NY¹Y²         (where R¹³ is hydrogen, cyano, alkyl, cycloalkyl or aryl), or         —N(R¹¹)—C(═Z)OR¹¹; L² represents a direct bond or a straight- or         branched-carbon chain comprising from 2 to about 6 carbon atoms         and contains a double or triple carbon-carbon bond; and R⁸ is         hydrogen, aryl, cycloalkenyl, cycloalkyl, heteroaryl or         heterocycloalkyl];     -   R⁴ represents a group —L³—R¹⁴         [where L³ represents a direct bond or a straight- or         branched-chain alkylene linkage containing from 1 to about 6         carbon atoms (optionally substituted by halogen, hydroxy, alkoxy         or oxo); and R¹⁴ is hydrogen, alkyl, azido, hydroxy, alkoxy,         aryl, arylalkyloxy, aryloxy, carboxy (or an acid bioisostere),         cycloalkyloxy, heteroaryl, heteroarylalkyloxy, heteroaryloxy,         heterocycloalkyl, heterocycloalkyloxy, nitro, —NY⁴Y⁵, {where Y⁴         and Y⁵ are independently hydrogen, aryl, cycloalkyl,         heterocycloalkyl, heteroaryl or alkyl optionally substituted by         alkoxy, aryl, cyano, cycloalkyl, heteroaryl, heteroxyxloalkyl,         hydroxy, oxo, —CO₂R¹⁰, —CONY¹Y² or —NY¹Y², or the group —NY⁴Y⁵         may form a 5-7 membered cyclic amine which (i) may be optionally         substituted with one or more substituents selected from alkoxy,         carboxamido, carboxy, hydroxy, oxo (or a 5, 6, or 7 membered         cyclic acetal derivative thereof), R⁹ or alkyl substituted by         carboxy, carboxamido or hydroxy (ii) may also contain a further         heteroatom selected from O, S, SO₂ or NY⁶ (where Y⁶ is hydrogen,         alkyl, aryl, arylalkyl, —C(═Z)R⁹, —C(═Z)OR⁹ or —SO₂R⁹) and (iii)         may also be fused to additional aryl, heteroaryl,         heterocycloalkyl or cycloalkyl rings to form a bicyclic or         tricyclic ring system}, —N(R¹⁰)—C(═Z)—R¹⁵ (where R¹⁵ is alkyl,         alkoxy, aryl, arylalkyloxy, cycloalkyl, heteroaryl,         heteroarylalkoxy or heterocycloalkyl); —N(R¹⁰)—C(═Z)—L⁴—R¹⁶         (where R¹⁶ is alkoxy, aryl, arylalkyloxy,         arylalkyloxycarbonylamino, carboxy (or an acid bioisotere),         cycloalkyl, cyano, halo, heteroaryl, heteroarylalkoxy,         heterocycloalkyl, hydroxy or —NY¹Y², and L⁴ is a straight- or         branched-chain alkylene linkage containing from 1 to about 6         carbon atoms), —NH—C(═Z)—NH—R¹⁵, —NH—C(═Z)—NH—L⁴—R¹⁶,         —N(R¹⁰)—SO₂—R¹⁵, —N(R¹⁰)—SO₂—L⁴—R¹⁶, —S(O)_(n)R⁹, —C(═Z)—NY⁴Y⁵         or —C(═Z)—OR⁹];     -   R⁵ represents hydrogen, alkyl or hydroxyalkyl; or     -   R⁴ and R⁵, when attached to the same carbon atom, may form with         the said carbon atom a cycloalkyl, cycloalkenyl or         heterocycloalkyl ring or a group C═CH₂;     -   R⁶ represents hydrogen or alkyl; and     -   m is zero or an integer 1 or 2;     -   and N-oxides thereof, and their prodrugs; and pharmaceutically         acceptable salts and solvates (e.g. hydrates) of compounds of         formula (I) and N-oxides thereof, and their prodrugs.

In the present specification, the term “compounds of the invention”, and equivalent expressions, are meant to embrace compounds of general formula (I) as hereinbefore described, which expression includes the N-oxides, the prodrugs, the pharmaceutically acceptable salts, and the solvates, e.g. hydrates, where the context so permits. Similarly, reference to intermediates, whether or not they themselves are claimed, is meant to embrace their N-oxides, salts, and solvates, where the context so permits. For the sake of clarity, particular instances when the context so permits are sometimes indicated in the text, but these instances are purely illustrative and it is not intended to exclude other instances when the context so permits.

It will be appreciated that when m is zero the cyclic acetal system in formula (I) represents a 1,3-dioxolane ring; when m is 1 the cyclic acetal system in formula (I) represents a 1,3-dioxane; and when m is 2 the cyclic acetal system in formula (I) represents a 1,3-dioxepane.

As used above, and throughout the description of the invention, the following terms, unless otherwise indicated, shall be understood to have the following meanings:

“Patient” includes both human and other mammals.

“Acid bioisostere” means a group which has chemical and physical similarities producing broadly similar biological properties to a carboxy group (see Lipinski, Annual Reports in Medicinal Chemistry, 1986, 21, page 283 “Bioisosterism In Drug Design”; Yun, Hwahak Sekye, 1993, 33, pages 576-579 “Application Of Bioisosterism To New Drug Design”; Zhao, Huaxue Tongbao, 1995, pages 34-38 “Bioisosteric Replacement And Development Of Lead Compounds In Drug Design”; Graham, Theochem, 1005, 343, pages 105-109 “Theoretical Studies Applied To Drug Design:ab initio Electronic Distributions In Bioisosteres”). Examples of suitable acid bioisosteres include: —C(═O)—NHOH, —C(═O)—CH₂OH, —C(═O)—CH₂SH, —C(═O)—NH—CN, sulpho, phosphono, alkylsulphonylcarbamoyl, tetrazolyl, arylsulphonylcarbamoyl, heteroarylsulphonylcarbamoyl, N-methoxycarbamoyl, 3-hydroxy-3-cyclobutene-1,2-dione, 3,5-dioxo-1,2,4-oxadiazolidinyl or heterocyclic phenols such as 3-hydroxyisoxazolyl and 3-hydroxy-1-methylpyrazolyl.

“Acyl” means an H—CO— or alkyl—CO— group in which the alkyl group is as described herein.

“Acylamino” is an acyl-NH— group wherein acyl is as defined herein.

“Alkenyl” means an aliphatic hydrocarbon group containing a carbon-carbon double bond and which may be straight or branched having about 2 to about 15 carbon atoms in the chain. Preferred alkenyl groups have 2 to about 12 carbon atoms in the chain; and more preferably about 2 to about 4 carbon atoms in the chain. “Branched”, as used herein and throughout the text, means that one or more lower alkyl groups such as methyl, ethyl or propyl are attached to a linear chain; here a linear alkenyl chain. “Lower alkenyl” means about 2 to about 4 carbon atoms in the chain which may be straight or branched. Exemplary alkenyl groups include ethenyl, propenyl, n-butenyl, i-butenyl, 3-methylbut-2-enyl, n-pentenyl, heptenyl, octenyl, cyclohexylbutenyl and decenyl.

“Alkoxy” means an alkyl-O— group in which the alkyl group is as described herein. Exemplary alkoxy groups include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy and heptoxy.

“Alkoxymethyl” means an alkyl-O—CH₂— group in which the alkyl group is as described herein. Exemplary alkoxymethyl groups include methoxymethyl and ethoxymethyl.

“Alkoxycarbonyl” means an alkyl-O—CO— group in which the alkyl group is as described herein. Exemplary alkoxycarbonyl groups include methoxy- and ethoxycarbonyl.

“Alkyl” means, unless otherwise specified, an aliphatic hydrocarbon group which may be straight or branched having about 1 to about 15 carbon atoms in the chain, optionally substituted by one or more halogen atoms. Particular alkyl groups have from 1 to about 6 carbon atoms. Exemplary alkyl groups for R⁵, R⁶ and within R⁴ include C₁₋₄alkyl groups such as methyl, ethyl, n-propyl and i-propyl.

“Alkylene” means a straight or branched bivalent hydrocarbon chain having from 1 to about 15 carbon atoms. Particular alkylene groups are the lower alkylene groups having from 1 to about 6 carbon atoms. Exemplary groups include methylene and ethylene.

“Alkylsulphinyl” means an alkyl-SO— group in which the alkyl group is as previously described. Preferred groups are those in which the alkyl group is C₁₋₄alkyl.

“Alkylsulphonyl” means an alkyl-SO₂— group in which the alkyl group is as previously described. Preferred groups are those in which the alkyl group is C₁₋₄alkyl.

“Alkylsulphonylcarbamoyl” means an alkyl-SO₂—NH—C(═O)— group in which the alkyl group is as previously described. Preferred alkylsulphonylcarbamoyl groups are those in which the alkyl group is C₁₋₄alkyl.

“Alkylthio” means an alkyl-S— group in which the alkyl group is as previously described. Exemplary alkylthio groups include methylthio, ethylthio, isopropylthio and heptylthio.

“Alkynyl” means an aliphatic hydrocarbon group containing a carbon-carbon triple bond and which may be straight or branched having about 2 to about 15 carbon atoms in the chain. Preferred alkynyl groups have 2 to about 12 carbon atoms in the chain; and more preferably about 2 to about 4 carbon atoms in the chain. Exemplary alkynyl groups include ethynyl, propynyl, n-butynyl, i-butynyl, 3-methylbut-2-ynyl, and n-pentynyl.

“Aroyl” means an aryl-CO— group in which the aryl group is as described herein. Exemplary groups include benzoyl and 1- and 2-naphthoyl.

“Aroylamino” is an aroyl-NH— group wherein aroyl is as previously defined.

“Aryl” as a group or part of a group denotes: (i) an optionally substituted monocyclic or multicyclic aromatic carbocyclic moiety of about 6 to about 14 carbon atoms, such as phenyl or naphthyl; or (ii) an optionally substituted partially saturated multicyclic aromatic carbocyclic moiety in which an aryl and a cycloalkyl or cycloalkenyl group are fused together to form a cyclic structure, such as a tetrahydronaphthyl, indenyl or indanyl ring. Aryl groups may be substituted with one or more aryl group substituents which may be the same or different, where “aryl group substituent” includes, for example, acyl, acylamino, alkoxy, alkoxycarbonyl, alkylenedioxy, alkylsulphinyl, alkylsulphonyl, alkylthio, aroyl, aroylamino, aryl, arylalkyloxy, arylalkyloxycarbonyl, arylalkylthio, aryloxy, aryloxycarbonyl, arylsulphinyl, arylsulphonyl, arylthio, carboxy, cyano, halo, heteroaroyl, heteroaryl, heteroarylalkyloxy, heteroaroylamino, heteroaryloxy, hydroxy, nitro, trifluoromethyl, Y⁷Y⁸N—, Y⁷Y⁸NCO—, Y⁷Y⁸NSO₂— (where Y⁷ and Y⁸ are independently hydrogen, alkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl), Y⁷Y⁸N—C₂₋₆alkylene-Z²— (where Z² is O, NR⁵ or S(O)_(n)), alkylC(═O)—Y⁷N—, alkylSO₂—Y⁷N— or alkyl optionally substituted with aryl, heteroaryl, hydroxy, or Y⁷Y⁸N—. Preferred aryl group substituents within R² include halogen, alkoxy, trifluoromethyl, alkylthio, alkylsulphinyl, Y⁷Y⁸N—, alkylC(═O)—Y⁷N— or alkylSO₂—Y⁷N—, more preferably fluoro.

“Arylalkyl” means an aryl-aryl-group in which the aryl moieties are as previously described. Preferred arylalkyl groups contain a C₁₋₄alkyl moiety. Exemplary arylalkyl groups include benzyl, 2-phenethyl and naphthlenemethyl.

“Arylalkyloxy” means an arylalkyl-O— group in which the arylalkyl groups is as previously described. Exemplary arylalkyloxy groups include benzyloxy and 1- or 2-naphthalenemethoxy.

“Arylalkyloxycarbonyl” means an arylalkyl-O—CO— group in which the arylalkyl groups is as previously described. An exemplary arylalkyloxycarbonyl group is benzyloxycarbonyl.

“Arylalkylthio” means an arylalkyl-S— group in which the arylalkyl group is as previously described. An exemplary arylalkylthio group is benzylthio.

“Aryloxy” means an aryl-O— group in which the aryl group is as previously described. Exemplary aryloxy groups include optionally substituted phenoxy and naphthoxy.

“Aryloxycarbonyl” means an aryl-O—CO— group in which the aryl group is as previously described. Exemplary aryloxycarbonyl groups include phenoxycarbonyl and naphthoxycarbonyl.

“Arylsulphinyl” means an aryl-SO— group in which the aryl group is as previously described.

“Arylsulphonyl” means an aryl-SO₂— group in which the aryl group is as previously described.

“Arylsulphonylcarbamoyl” means an aryl-SO₂—NH—C(═O)— group in which the aryl group is as previously described.

“Arylthio” means an aryl-S— group in which the aryl group is as previously described. Exemplary arylthio groups include phenylthio and naphthylthio.

“Azaheteroaryl” means an aromatic carbocyclic moiety of about 5 to about 10 ring members in which one of the ring members is nitrogen and the other ring members are chosen from carbon, oxygen, sulphur, or nitrogen. Examples of optionally substituted azaheteroaryl groups include pyridyl, pyrimidinyl, quinolinyl, isoquinolinyl, quinazolinyl, imidazolyl, and benzimidazolyl, optionally substituted with one or more “heteroaryl group substituents”. Preferred azaheteroaryl groups within R¹ include optionally substituted pyridyl and pyrimidinyl. Preferred heteroaryl group substituents when R¹ is pyrimidinyl include R¹⁷Z³— [where R¹⁷ is alkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, or alkyl substituted by alkoxy, aryl, cyano, cycloalkyl, heteroaryl, heterocycloalkyl, hydroxy, oxo, —CO₂R¹⁰, —CONY¹Y² or —NY⁴Y⁵ and Z³ is O or S(O)_(n)] and Y⁴Y⁵N—.

“Cycloalkenyl” means an optionally substituted non-aromatic monocyclic or multicyclic ring system containing at least one carbon-carbon double bond and having about 5 to about 10 carbon atoms. Exemplary monoclylic cycloalkenyl rings include cyclopentenyl, cyclohexenyl and cyclopentenyl.

Exemplary multicyclic cycloalkenyl ring include norbornenyl. The cycloalkenyl group may be substituted by one or more substituents chosen from, for example, halo, or alkyl.

“Cycloalkoxymethyl” means a cycloalkyl-O—CH₂— group in which the cycloalkyl group is as described hereinafter. Exemplary cycloalkoxymethyl groups include cyclopropyloxymethyl and cyclopentyloxymethyl.

“Cycloalkyl” means an optionally substituted non-aromatic monocyclic or multicyclic ring system of about 3 to about 10 carbon atoms. Exemplary monocyclic cycloalkyl rings include cyclopropyl, cyclopentyl, cyclohexyl and cycloheptyl. Exemplary multicyclic cycloalkyl rings include perhydronaphthyl, adamant-(1- or 2-)yl and norbornyl and spirocyclic groups e.g. spiro[4,4]non-2yl. When R³ is, or contains, a cycloalkyl ring this may particularly represent a 3 to 7 membered monocyclic ring, especially cyclohexyl. The cycloalkyl group may be substituted by one or more (e.g. 1, 2, or 3) substituents chosen from, for example, alkyl, aryl, arylalkyl, halo, halo substituted alkyl (such as trifluoromethyl), hydroxyalkyl, hydroxy, alkoxy, —S(O)_(n)-alkyl, —NY¹Y² or —CO₂R¹².

“Cycloalkylalkyl” means a cycloalkyl-alkyl-group in which the cycloalkyl and alkyl moieties are as previously described. Exemplary monocyclic cycloalkylalkyl groups include cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl and cycloheptylmethyl.

“Cycloalkyloxy” means a cycloalkyl-O— group in which the cycloalkyl group is as described herein. Exemplary cycloalkyloxy groups include cyclopropyloxy, cyclopentyloxy, cyclohexyloxy and cycloheptyloxy.

“Halo” or “halogen” means fluoro, chloro, bromo, or iodo. Preferred are fluoro or chloro.

“Heteroaroyl” means a heteroaryl-CO— group in which the heteroaryl group is as described herein. Exemplary groups include pyridylcarbonyl.

“Heteroaroylamino” means a heteroaroyl-NH— group in which the heteroaroyl moiety is as previously described.

“Heteroaryl” as a group or part of a group denotes an optionally substituted aromatic monocyclic or multicyclic organic moiety of about 5 to about 10 ring members in which one or more of the ring members is/are element(s) other than carbon, for example nitrogen, oxygen or sulphur. Examples of suitable optionally substituted heteroaryl groups include benzimidazolyl, furyl, imidazolyl, isoxazolyl, isoquinolinyl, isothiazolyl, oxadiazolyl, pyrazinyl, pyridazinyl, pyrazolyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, 1,3,4-thiadiazolyl, thiazolyl, thienyl and triazolyl groups. When R¹ is an optionally substituted heteroaryl group this may particularly represent an optionally substituted “azaheteroaryl” group. Heteroaryl groups may be substituted with one or more heteroaryl group substituents which may be the same or different, where “heteroaryl group substituent” includes, for example acyl, acylamino, alkoxycarbonyl, alkylenedioxy, aroyl, aroylamino, aryl, arylalkyloxycarbonyl, aryloxycarbonyl, carboxy, cyano, halo, heteroaroyl, heteroaryl, heteroaroylamino, hydroxy, nitro, trifluoromethyl, R¹⁷Z³—, Y⁴Y⁵N—, Y⁴Y⁵N—CO—, Y⁴Y⁵NSO₂—, alkylSO₂—Y⁴N— or alkyl optionally substituted with aryl, heteroaryl, hydroxy, oxo, —CO₂R¹⁰, —CONY¹Y² or Y⁴Y⁵N—.

“Heteroarylalkyl” means a heteroaryl-alkyl-group in which the heteroaryl and alkyl moieties are as previously described. Preferred heteroarylalkyl groups contain a C₁₋₄alkyl moiety. Exemplary heteroarylalkyl groups include pyridylmethyl.

“Heteroarylalkyloxy” means an heteroarylalkyl-O— group in which the heteroarylalkyl group is as previously described. Exemplary heteroaryloxy groups include optionally substituted pyridylmethoxy.

“Heteroaryloxy” means an heteroaryl-O— group in which the heteroaryl group is as previously described. Exemplary heteroaryloxy groups include optionally substituted pyridyloxy.

“Heteroarylsulphonylcarbamoyl” means a heteroaryl-SO₂—NH—C(═O)— group in which the heteroaryl group is as previously described.

“Heterocycloalkyl” means a cycloalkyl group of about 3 to 7 ring members which contains one or more heteroatoms selected from O, S or NY³. Exemplary heterocycloalkyl groups include 5-7 membered cyclic ethers such as tetrahydrofuran and perhydropyran.

“Heterocycloalkylalkyl” means a heterocycloalkyl-alkyl-group in which the heterocycloalkyl and alkyl moieties are as previously described.

“Heterocycloalkyloxy” means a heterocycloalkyl-O— group in which the heterocycloalkyl is as previously defined.

“Hydroxyalkyl” means a HO-alkyl-group in which alkyl is as previously defined. Preferred hydroxyalkyl groups contain C₁₋₄alkyl. Exemplary hydroxyalkyl groups include hydroxymethyl and 2-hydroxyethyl.

“Y⁷Y⁸N—” means a substituted or unsubstituted amino group, wherein Y⁷ and Y⁸ are as previously described. Exemplary groups include amino (H₂N—), methylamino, ethylmethylamino, dimethylamino and diethylamino.

“Y⁷Y⁸NCO—” means a substituted or unsubstituted carbamoyl group, wherein Y⁷ and Y⁸ are as previously described. Exemplary groups are carbamoyl (H₂NCO—) and dimethylcarbamoyl (Me₂NCO—).

“Y⁷Y⁸NSO₂—” means a substituted or unsubstituted sulphamoyl group, wherein Y⁷ and Y⁸ are as previously described. Exemplary groups are sulphamoyl (H₂NSO₂—) and dimethylsulphamoyl (Me₂NSO₂—).

“Prodrug” means a compound which is convertible in vivo by metabolic means (e.g. by hydrolysis) to a compound of formula (I), including N-oxides thereof. For example an ester of a compound of formula (I) containing a hydroxy group may be convertible by hydrolysis in vivo to the parent molecule. Alternatively an ester of a compound of formula (I) containing a carboxy group may be convertible by hydrolysis in vivo to the parent molecule.

“Solvate” means a physical association of a compound of this invention with one or more solvent molecules. This physical association includes hydrogen bonding. In certain instances the solvate will be capable of isolation, for example when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid. “Solvate” encompasses both solution-phase and isolable solvates. Representative solvates include hydrates, ethanolates, methanolates, and the like.

Suitable esters of compounds of formula (I) containing a hydroxy group, are for example acetates, citrates, lactates, tartrates, malonates, oxalates, salicylates, propionates, succinates, fumarates, maleates, methylene-bis-b-hydroxynaphthoates, gentisates, isethionates, di-p-toluoyltartrates, methanesulphonates, ethanesulphonates, benzenesulphonates, p-toluenesulphonates, cyclohexylsulphamates and quinates.

Suitable esters of compounds of formula (I) containing a carboxy group, are for example those described by F. J. Leinweber, Drug Metab. Res., 1987, 18, page 379.

An especially useful class of esters of compounds of formula (I) containing a hydroxy group, may be formed from acid moieties selected from those described by Bundgaard et. al., J. Med. Chem., 1989, 32, page 2503-2507, and include substituted (aminomethyl)-benzoates, for example dialkylamino-methylbenzoates in which the two alkyl groups may be joined together and/or interrupted by an oxygen atom or by an optionally substituted nitrogen atom, e.g. an alkylated nitrogen atom, more especially (morpholino-methyl)benzoates, e.g. 3- or 4-(morpholinomethyl)-benzoates, and (4-alkylpiperazin-1-yl)benzoates, e.g. 3- or 4-(4-alkylpiperazin-1-yl)benzoates.

Some of the compounds of the present invention are basic, and such compounds are useful in the form of the free base or in the form of a pharmaceutically acceptable acid addition salt thereof.

Acid addition salts are a more convenient form for use; and in practice, use of the salt form inherently amounts to use of the free base form. The acids which can be used to prepare the acid addition salts include preferably those which produce, when combined with the free base, pharmaceutically acceptable salts, that is, salts whose anions are non-toxic to the patient in pharmaceutical doses of the salts, so that the beneficial inhibitory effects inherent in the free base are not vitiated by side effects ascribable to the anions. Although pharmaceutically acceptable salts of said basic compounds are preferred, all acid addition salts are useful as sources of the free base form even if the particular salt, per se, is desired only as an intermediate product as, for example, when the salt is formed only for purposes of purification, and identification, or when it is used as intermediate in preparing a pharmaceutically acceptable salt by ion exchange procedures. Pharmaceutically acceptable salts within the scope of the invention include those derived from mineral acids and organic acids, and include hydrohalides, e.g. hydrochlorides and hydrobromides, sulphates, phosphates, nitrates, sulphamates, acetates, citrates, lactates, tartrates, malonates, oxalates, salicylates, propionates, succinates, fumarates, maleates, methylene-bis-b-hydroxynaphthoates, gentisates, isethionates, di-p-toluoyltartrates, methane-sulphonates, ethanesulphonates, benzenesulphonates, p-toluenesulphonates, cyclohexylsulphamates and quinates.

Where the compound of the invention is substituted with an acidic moiety, base addition salts may be formed and are simply a more convenient form for use; and in practice, use of the salt form inherently amounts to use of the free acid form. The bases which can be used to prepare the base addition salts include preferably those which produce, when combined with the free acid, pharmaceutically acceptable salts, that is, salts whose cations are non-toxic to the patient in pharmaceutical doses of the salts, so that the beneficial inhibitory effects inherent in the free base are not vitiated by side effects ascribable to the cations. Pharmaceutically acceptable salts, including those derived from alkali and alkaline earth metal salts, within the scope of the invention include those derived from the following bases: sodium hydride, sodium hydroxide, potassium hydroxide, calcium hydroxide, aluminium hydroxide, lithium hydroxide, magnesium hydroxide, zinc hydroxide, ammonia, ethylenediamine, N-methyl-glucamine, lysine, arginine, ornithine, choline, N,N′-dibenzylethylenediamine, chloroprocaine, diethanolamine, procaine, N-benzylphenethylamine, diethylamine, piperazine, tris(hydroxymethyl)aminomethane, tetramethylammonium hydroxide, and the like.

As well as being useful in themselves as active compounds, salts of compounds of the invention are useful for the purposes of purification of the compounds, for example by exploitation of the solubility differences between the salts and the parent compounds, side products and/or starting materials by techniques well known to those skilled in the art.

With reference to formula (I) above, the following are particular and preferred groupings:

R¹ may particularly represent optionally substituted azaheteroaryl such as optionally substituted pyridyl, pyrimidinyl, quinolinyl, isoquinolinyl, quinazolinyl, imidazolyl or benzimidazolyl (for example optionally substituted 4-pyridyl, 4-pyrimidinyl, 4-quinolinyl, 6-isoquinolinyl, 4-quinazolinyl, 1-imidazolyl or 1-benzimidazolyl). R¹ is preferably optionally substituted 4-pyridyl or 4-pyrimidinyl, especially unsubstituted 4-pyridyl or 2-substituted 4-pyrimidinyl. Preferred substituents include C₁₋₄alkyl, especially methyl, —NY⁴Y⁵ (especially where at least one of Y⁴ and Y⁵ is hydrogen) or —OR¹⁷ (especially where R¹⁷ is cycloalkyl).

R² is preferably optionally substituted phenyl, particularly when substituted by halogen, especially fluoro and chloro, or an alkylthio or alkylsulphinyl group, especially methylthio or methysulphinyl, or a trifluoromethyl group. R² is more preferably phenyl substituted by a halogen (e.g. fluorine) atom, especially in the 4-position.

R³ may particularly represent hydrogen or C₁₋₄alkyl, preferably hydrogen.

R⁴ may particularly represent a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —NY⁴Y⁵, where Y⁴ and Y⁵ are as defined hereinbefore, especially where Y⁴ and Y⁵ are hydrogen.

R⁴ may also particularly represent a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —N(R¹⁰)—C(═Z)—R¹⁵, in which Z, R¹⁰ and R¹⁵ are as defined hereinbefore, especially where Z is oxygen, R¹⁰ is hydrogen and R¹⁵ is alkyl (especially methyl), aryl (e.g. substituted or more preferably, unsubstituted phenyl) or heteroaryl.

R⁴ may also particularly represent a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —N(R¹⁰)—C(═Z)—L⁴—R¹⁶, in which Z, L⁴, R¹⁰ and R¹⁶ are as defined hereinbefore, especially where Z is oxygen, L⁴ is methylene, R¹⁰ is hydrogen, and R¹⁶ is aryl (e.g. substituted or more preferably, unsubstituted phenyl) or heteroaryl.

R⁴ may also particularly represent a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —C(═Z)NY⁴Y⁵, in which Z is as defined hereinbefore, especially oxygen, and Y⁴ and Y⁵ are as defined hereinbefore, especially where Y⁴ and Y⁵ are hydrogen or where Y⁴ is hydrogen and Y⁵ is aryl, arylalkyl, heteroaryl or heteroarylalkyl.

R⁴ may also particularly represent a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —C(═Z)—NY⁴Y⁵, in which Z is as defined hereinbefore, especially oxygen, and the group —NY⁴Y⁵ forms a 5-7 membered cyclic amine [which may optionally contain a further heteroatom selected from O, S or NY⁶ (where Y⁶ is as defined hereinbefore)], preferably a 5-7 membered cyclic amine optionally containing oxygen, especially a morpholine ring.

R⁴ may also particularly represent a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —C(═Z)—OR⁹, in which Z and R⁹ are as defined hereinbefore, especially where Z is oxygen and R⁹ is C₁₋₄alkyl, preferably methyl.

R⁴ may also particularly represent a group —L³—R¹⁴ where L³ is a direct bond, especially methylene or ethylene, and R¹⁴ is alkyl, especially methyl.

R⁴ may also particularly represent a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is hydroxy.

R⁴may also particularly represent a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —N(R¹⁰)—C(═Z)—R¹⁵, in which Z, R¹⁰ and R¹⁵ are as defined hereinbefore, especially where Z is oxygen, R¹⁰ is hydrogen and R¹⁵ is alkyl, aryl or heteroaryl.

R⁴ may also particularly represent a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —N(R¹⁰)—C(═Z)—L⁴—R¹⁶, in which Z, L⁴, R¹⁰ and R¹⁵ are as defined hereinbefore, especially where Z is oxygen, L⁴ is C₁₋₆alkylene, especially methylene, R¹⁰ is hydrogen and R¹⁶ is aryl or heteroaryl.

R⁴ may also particularly represent a group —L³—R¹⁴ where L³ is C₁₋₆-alkylene, especially methylene, and R¹⁴ is —NHC(═Z)—NH—R¹⁵, in which Z and R¹⁵ are as defined hereinbefore, especially where R¹⁵ is alkyl, aryl or heteroaryl.

R⁴ may also particularly represent a group —L—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —NH—C(═Z)—NH—L⁴—R¹⁶, in which Z, L⁴ and R¹⁶ are as defined hereinbefore, especially where L⁴ is methylene and R¹⁵ is aryl or heteroaryl.

R⁴ may also particularly represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially C₁₋₃alkylene, preferably methylene, and R¹⁴ is —NY⁴Y⁵ are as defined hereinbefore, especially where Y⁴ and Y⁵ are hydrogen.

R⁴ may also particularly represent a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene or ethylene, and R¹⁴ is aryl or heteroaryl.

R⁴ may also particularly represent a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —N(R¹⁰)—SO₂—R¹⁵, in which R¹⁰ and R¹⁵ are as defined hereinbefore, especially where R¹⁰ is hydrogen and R¹⁵ is alkyl, aryl or heteroaryl.

R⁴ may also particularly represent a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —N(R¹⁰)—SO₂—L⁴—R¹⁵, in which L⁴, R¹⁰ and R¹⁵ are as defined hereinbefore, especially where L⁴ is methylene , R¹⁰ is hydrogen and R¹⁵ is alkyl, aryl or heteroaryl.

R⁵ may particularly represent hydrogen or C₁₋₄alkyl, especially methyl.

R⁵ may also particularly represent hydroxylalkyl, especially hydroxymethyl.

R⁴ and R⁵ together with the carbon atom to which they are attached may particularly represent a group C═CH₂ or a 5-7 membered cyclic ether such as tetrahydrofuran-2-yl or perhydropyran-2-yl.

R⁶ may particularly represent hydrogen or C₁₋₄alkyl, especially hydrogen.

m is preferably an integer 1.

It is to be understood that this invention covers all appropriate combinations of the particular and preferred groupings referred to herein.

A particular group of components of the invention are compounds of formula (Ia):

in which R⁴ and R⁵ are as hereinabove defined, and N-oxides thereof, and their prodrugs; and pharmaceutically acceptable salts and solvates (e.g. hydrates) of compounds of formula (Ia) and N-oxides thereof, and their prodrugs.

Compounds of formula (Ia) in which R⁴ represents a group —L³—R¹⁴ is a direct bond and R¹⁴ is —NY⁴Y⁵, and Y⁴ and Y⁵ are as defined hereinbefore, especially where Y⁴ and Y⁵ are hydrogen, are preferred.

Compounds of formula (Ia) in which R⁴ represents a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —N(R¹⁰)—C(═Z)—R¹⁵, in which Z, R¹⁰ and R¹⁵ are as defined hereinbefore, especially where Z is oxygen, R¹⁰ is hydrogen and R¹⁵ is alkyl (especially methyl), aryl (e.g. substituted or more preferably, unsubstituted phenyl) or heteroaryl, are also preferred.

Compounds of formula (Ia) in which R⁴ represents a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —N(R¹⁰)—C(═Z)—L⁴—R¹⁶, in which Z, L⁴, R¹⁰ and R¹⁶ are as defined hereinbefore, especially where Z is oxygen, L⁴ is methylene, R¹⁰ is hydrogen and R¹⁶ is aryl (e.g. substituted or more preferably, unsubstituted phenyl) or heteroaryl), are also preferred.

Compounds of formula (Ia) in which R⁴ represents a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —C(═Z)—NY⁴Y⁵, in which Z is as defined hereinbefore, especially oxygen, and Y⁴ and Y⁵ are as defined hereinbefore, especially where Y⁴ and Y⁵ are hydrogen or where Y⁴ is hydrogen and Y⁵ is aryl, heteroaryl or heteroarylalkyl, are also preferred.

Compounds of formula (Ia) in which R⁴ represents a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —C(═Z)—NY⁴Y⁵, in which Z is as defined hereinbefore, especially oxygen, and the group —NY⁴Y⁵ forms a 5-7 membered cyclic amine [which may optionally contain a further heteroatom selected from O, S or NY⁶ (where Y⁶ is as defined hereinbefore)], preferably a 5-7 membered cyclic amine optionally containing oxygen, especially a morpholine ring, are also preferred.

Compounds of formula (Ia) in which R⁴ represents a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —C(═Z)—OR⁹, in which Z and R⁹ are as defined hereinbefore, especially where Z is oxygen and R⁹ is C₁₋₄alkyl, preferably, methyl, are also preferred.

Compounds of formula (Ia) in which R⁴ represents a group —L³—R¹⁴ where L³ is a direct bond, especially methylene or ethylene, and R¹⁴ is alkyl, especially methyl, are also preferred.

Compounds of formula (Ia) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is hydroxy, are also preferred.

Compounds of formula (Ia) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —N(R¹⁰)—C(═Z)—R¹⁵, in which Z, R¹⁰ and R¹⁵ are as defined hereinbefore, especially where Z is oxygen, R¹⁰ is hydrogen and R¹⁵ is alkyl, aryl or heteroaryl, are also preferred.

Compounds of formula (Ia) in which R⁴ represents group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —N(R¹⁰)—C(═Z)—L⁴—R¹⁶, in which Z, L⁴, R¹⁰ and R¹⁵ ae as defined hereinbefore, especially where Z is oxygen, L⁴ is C₁₋₆alkylene, especially methylene, R¹⁰ is hydrogen and R¹⁶ is aryl or heteroaryl, are also preferred.

Compounds of formula (Ia) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —NH—C(═Z)—NH—R¹⁵, in which Z and R¹⁵ are as defined hereinbefore, especially where R¹⁵ is alkyl, or aryl or heteroaryl, are also preferred.

Compounds of formula (Ia) in which R⁴ represents group —L³—L¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —NH—C(═Z)—NH—L⁴—R¹⁶, in which Z, L⁴ and R¹⁶ are as defined hereinbefore, especially where L⁴ is methylene and R¹⁵ is aryl or heteroaryl, are also preferred.

Compounds of formula (Ia) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially C₁₋₃-alkylene, preferably methylene, and R¹⁴ is —NY⁴Y⁵, where Y⁴ and Y⁵ are as defined hereinbefore, especially where Y⁴ and Y⁵ are hydrogen, are also preferred.

Compounds of formula (Ia) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene or ethylene, and R¹⁴ is aryl or heteraryl, are also preferred.

Compounds of formula (Ia) in which R¹⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —N(R¹⁰)—SO₂—R¹⁵, in which R¹⁰ and R¹⁵ are as defined hereinbefore, especially where R¹⁰ is hydrogen and R¹⁵ is alkyl, aryl or heteroaryl, are also preferred.

Compounds of formula (Ia) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —N(R¹⁰)—SO₂—L⁴—R¹⁵, in which L⁴, R¹⁰ and R¹⁵ are as defined hereinbefore, especially where L⁴ is methylene, R¹⁰ is hydrogen and R¹⁵ is alkyl, aryl or heteroaryl, are also preferred.

Compounds of formula (Ia) in which R⁵ represents hydrogen, C₁₋₄alkyl (e.g. methyl) or hydroxyC₁₋₄alkyl (e.g. hydroxymethyl), especially methyl, are preferred.

Compounds of formula (Ia) in which R⁴ and R⁵ together with the carbon atom to which they are attached represent a group C═CH₂ or a 5-7 membered cyclic ether such as tetrahydrofuran-2-yl or perhydropyran-2-yl are also preferred.

A preferred group of compounds of the invention are compounds of formula (Ia) in which R⁴ is a group —L³—R¹⁴ (where L³ is a direct bond and R¹⁴ is (i) —NY⁴Y⁵, preferably —NH₂; (ii) —N(R¹⁰)—C(═Z)—R¹⁵, preferably —NH—C(═O)-alkyl, —NH—C(═O)-aryl or —NH—C(═O)-heteroaryl, especially —NH—C(═O)-aryl, particularly where aryl is substituted, or more preferably, unsubstitued phenyl; (iii) —N(R¹⁰)—C(═Z)—L⁴—R¹⁶, preferably —NH—C(═O)—CH₂-aryl or —NH—C(═O)—CH₂-heteroaryl, particularly where aryl is substituted, or more preferably, unsubstituted phenyl; (iv) —C(═Z)—NY⁴Y⁵, preferably —C(═O)—NH₂; (v) —C(═Z)—NY⁴Y⁵, preferably —C(═O)—NY⁴Y⁵ where the group —NY⁴Y⁵ forms a 5-7 membered cyclic amine [which may optionally contain a further heteroatom selected from O, S or NY⁶ (where Y⁶ is a defined hereinbefore), preferably a 5-7 membered cyclic amine optionally containing oxygen, especially a morpholine ring]; (vi) —C(═Z)OR⁹, particularly —CO₂Me; or (vii) alkyl, especially methyl}and R⁵ represents hydrogen, C₁₋₄alkyl (e.g. methyl) or hydroxyC₁₋₄alkyl (e.g. hydroxymethyl), especially methyl; and N-oxides thereof, and their prodrugs; and pharmaceutically acceptable salts and solvates (e.g. hydrates) of compounds of formula (Ia) herein and N-oxides thereof, and their prodrugs.

A further preferred group of compounds of formula (Ia) are compounds in which R⁴ is a group —L³—R¹⁴ {where L³ is a methylene linkage and R¹⁴ is (i) hydroxy; (ii) —N(R¹⁰)—C(═Z)—R¹⁵, preferably —NH—C(═O)-alkyl, —NH—C(═O)-aryl or —NH—C(═O)-heteroaryl; (iii) —N(R¹⁰)—C(═Z)—L⁴—R¹⁶, preferably —NH—C(═O)—CH₂-aryl or —NH—C(═O)—CH₂-heteroaryl; (iv) —NH—C(═Z)—NH—R¹⁵ preferably —NH—C(═O)—NH-alkyl, —NH—C(═O)—NH-aryl or —NH—C(═O)—NH-heteroaryl; (v) NH—C(═Z)—NH—L⁴—R¹⁶ preferably —NH—C(═O)—NH—CH₂-alkyl, —NH—C(═O)—NH—CH₂aryl or —NH—C(═O)—NH—CH₂-heteroaryl; (vi) —NY⁴Y⁵, preferably —NH₂; (vii) aryl; (viii) heteroaryl; (ix) —N(R¹⁰)—SO₂—R¹⁵, preferably —NH—SO₂-alkyl, NH—SO₂-aryl or —NH—SO₂-heteoraryl} and R⁵ represent hydrogen, C₁₋₄alkyl (e.g. methyl) or hydroxyC₁₋₄alkyl (e.g. hydroxymethyl), especially methyl; and N-oxides thereof, and their prodrugs; and pharmaceutically acceptable salts and solvates (e.g. hydrates) of compounds of formula (Ia) herein and N-oxides thereof, and their prodrugs.

A further particular group of compounds of the invention are compounds of formula (Ib);

in which R⁴ and R⁵ are as hereinbefore defined, and R¹⁸ is R¹⁷Z³—or Y⁴Y⁵N—(in which R¹⁷, Y⁴, Y⁵ and Z³ are as hereinbefore defined), and N-oxides thereof, and their prodrugs; and pharmaceutically acceptable salts and solvates (e.g. hydrates) of compounds of formula (Ib) and N-oxides, thereof, and their prodrugs.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —NY⁴Y⁵, where Y⁴ and Y⁵ are as defined hereinbefore, especially where Y⁴ and Y⁵ are hydrogen, are preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —N(R¹⁰)—C(═Z)—R¹⁵, in which Z, R¹⁰ and R¹⁵ are as defined hereinbefore, especially where Z is oxygen, R¹⁰ is hydrogen and R¹⁵ is alkyl, (especially methyl) aryl (e.g. substituted or more preferably, unsubstitued phenyl) or heteroaryl, are also preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —N(R¹⁰)—C(═Z)—L⁴—R¹⁶, in which Z, L⁴, R¹⁰ and R¹⁶ are as defined hereinbefore, especially where Z is oxygen, L⁴ is methylene, R¹⁰ is hydrogen, and R¹⁶ is aryl (e.g. substituted or more preferably, unsubstituted phenyl) or heteroaryl, are also preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —C(═)—NY⁴Y⁶, in which Z is defined hereinbefore, especially oxygen, and Y⁴ and Y⁵ are as defined hereinbefore, especially where Y⁴ and Y⁵ are hydrogen or where Y⁴ is hydrogen and Y⁵ is aryl, heteoaryl or heteoarylalkyl, are also preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —C(═Z)—NY⁴Y⁵, in which Z is as defined hereinbefore, especially oxygen, and the group —NY⁴Y⁵ forms a 5-7 membered cyclic amine [which may optionally contain a further heteroatom selected from O, S or NY⁶ (where Y⁶ is as defined hereinbefore)], preferably a 5-7 member cyclic amine optionally containing oxygen, especially a morpholine ring, are also preferred

Compounds of formula (Ib) in which R⁴ represents group —L³—R¹⁴ where L³ is a direct bond and R¹⁴ is —C(═Z)—OR⁹, in which Z and R⁹ are as defined hereinbefore, especially where Z is oxygen and R⁹ is C₁₋₄alkyl, preferably methyl, are also preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is a direct bond, especially methylene or ethylene, and R¹⁴ is alkyl, especially methyl, are also preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is hydroxy, are also preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —N(R¹⁰)—C(═Z)—R¹⁵, in which Z, R¹⁰ and R¹⁵ are as defined hereinbefore, especially where Z is oxygen, R¹⁰ is hydrogen and R¹⁵ is alkyl, aryl or heteroaryl, are also preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —N(R¹⁰)—C(═Z)—L⁴—R¹⁶, in which Z, L⁴, R¹⁰ and R¹⁵ are as defined hereinbefore, especially where Z is oxygen, L⁴ is C₁₋₆alkylene, especially methylene, R¹⁰ is hydrogen and R¹⁶ is aryl or heteroaryl are also preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —NH—C(═Z)—NH—R¹⁵, in which Z and R¹⁵ are as defined hereinbefore, especially where R¹⁵ is alkyl, aryl or heteroaryl, are also preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —NH—C(═Z)—NH—L⁴R¹⁶, in which Z, L⁴ and R¹⁶ are as defined hereinbefore, especially where L⁴ is methylene and R¹⁵ is aryl or heteroaryl, are also preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially C₁₋₃alkylene, preferably methylene, and R¹⁴ is —NY⁴Y⁵, where Y⁴ and Y⁵ are as defined hereinbefore, especially where Y⁴ and Y⁵ are hydrogen, are also preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R⁴ where L³ is C₁₋₆alkylene, especially methylene or ethylene, and R¹⁴ is aryl or heteroaryl, are also preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene and R¹⁴ is —N(R¹⁰)—SO₂—R¹⁵, in which R¹⁰ and R¹⁵ are as defined hereinbefore, especially where R¹⁰ is hydrogen and R¹⁵ is alkyl, aryl or heteroaryl, are also preferred.

Compounds of formula (Ib) in which R⁴ represents a group —L³—R¹⁴ where L³ is C₁₋₆alkylene, especially methylene, and R¹⁴ is —N(R¹⁰)—SO₂—L⁴—R¹⁵, in which L⁴, R¹⁰ are R¹⁵ are as defined hereinbefore, especially where L⁴ is methylene, R¹⁰ is hydrogen and R¹⁵ is alkyl, aryl or heteroaryl, are also preferred.

Compounds of formula (Ib) in which R⁵ represents hydrogen, C₁₋₄alkyl (e.g. methyl) or hydroxyC₁₋₄alkyl (e.g. hydroxymethyl), especially methyl, are preferred.

Compounds of formula (Ib) in which R⁴ and R⁵ together with the carbon atom to which they are attached represent a group C═CH₂ or a 5-7 membered cyclic ether such as tetrahydrofuran-2-yl or perhydropyran-2-yl are also preferred.

Compounds of formula (Ib) in which R¹⁸ is —NY⁴Y⁵, where Y⁴ and Y⁵ are as hereinbefore defined, especially where Y⁴ is hydrogen Y⁵ is (i) arylalkyl, particularly optionally substituted benzyl or optionally substituted αmethylbenzyl (in which the phenyl group may be optionally substituted by one or more aryl group substituents, especially halo, methoxy, trifluoromethyl, methyl and methylenedioxy); (ii) heteroarylalkyl, particularly azaheteroaryl-alkyl, more particularly azaheteroaryl-CH₂; (iii) C₂₋₆alkyl substituted by alkoxy, particularly C₂₋₆alkyl substituted by methoxy; (iv) C₂₋₆alkyl substituted by —NY¹Y², particularly C₂₋₆alkyl substituted by —NMe₂; (v) C₂₋₆alkyl substituted by hydroxy; (vi) cycloalkyl or (vii) aryl, especially phenyl optionally substituted by one or more aryl group substituents, especially halo, methoxy, trifluoromethyl, methyl or methylenedioxy, are preferred.

Compounds of formula (Ib) in which R¹⁸ is —OR¹⁷, where R¹⁷ is as hereinbefore defined, especially where R¹⁷ is alkyl, aryl (especially phenyl optionally substituted by one or more aryl group substituents, especially halo, methoxy, trifluoromethyl, methyl or methylenedioxy) or cycloalkyl, are also preferred.

A preferred group of compounds of the invention are compounds of formula (Ib) in which R⁴ is a group, —L⁴—R¹⁴ (where L³ is a direct bond and R¹⁴ is (i) —NY⁴Y⁵, preferably —NH₂; (ii) —N(R¹⁰)—C(═Z)—R¹⁵, preferably —NH—C(═O)-alkyl, —NH—C(═O)-aryl or —NH—C(═O)-heteroaryl, especially —NH—C(═O)-aryl, particularly where aryl is substituted, or more preferably, unsubstituted phenyl; (iii) —N(R¹⁰)—C(═Z)—L⁴—R¹⁶, preferably —NH—C(═O)—CH₂-aryl or —NH—C(═O)—CH₂-heteroaryl, particularly where aryl is substituted, or more preferably, unsubstituted phenyl; (iv) —C(═Z)—NY⁴Y⁵, preferably —C(═O)—NH₂; (v) —C(═Z)—NY⁴Y⁵, preferably —C(═O)—NY⁴Y⁵ where the group —NY⁴Y⁵ forms a 5-7 membered cyclic amine [which may optionally contain a further heteroatom selected from O, S or NY⁶ (where Y⁶ is as defined hereinbefore), preferably a 5-7 membered cyclic amine optionally containing oxygen, especially a morpholine ring]; (vi) —C(═Z)OR⁹, particularly —CO₂Me; or (vii) alkyl, especially methyl]

R⁵ represents hydrogen, C₁₋₄alkyl (e.g. methyl) or hydroxyC₁₋₄alkyl (e.g. hydroxyl), especially methyl and R¹⁸ represents —NY⁴Y⁵ {where Y⁴ Y⁵ are as hereinbefore defined, especially where Y⁴ is hydrogen and Y⁵ is (i) arylalkyl, particularly benzyl or α-methylbenzyl; (ii) heteroarylalkyl, particularly azaheteroaryl-alkyl, more particularly azaheteroaryl-CH₂; (iii) C₂₋₆alkyl substituted by alkoxy, particularly C₂₋₆alkyl substituted by methoxy, (iv) C₂₋₆alkyl substituted by NY¹Y², particularly C₂₋₆alkyl substituted by —NMe₂; C₂₋₆alkyl substituted by hydroxy; (vi) cycloalkyl or (vii) aryl, especially phenyl optionally substituted by one or more aryl group substituents, especially halo, methoxy, trifluoromethyl, methyl or methylenedioxy} or —OR¹⁷, where ¹⁷ is alkyl or cycloalkyl; and N-oxides thereof, and their prodrugs; and pharmaceutically acceptable salts and solvates (e.g. hydrates) of compounds of formula (Ia) herein and N-oxides thereof, and their prodrugs.

A further preferred group of compounds of formula (Ib) are compounds in which R⁴ is a group —L³—R¹⁴ {where L³ is a methylene linkage and R¹⁴ is (i) hydroxy; (ii) —N(R¹⁰)—C(═Z)—R¹⁵, preferably —NH—C(═O)-alkyl, —NH—C(═O)-aryl or —NH—C(═O)-heteroaryl; (iii) —N(R¹⁰)—C(═Z)—L⁴R¹⁶, preferably —NH—C(═O)—CH₂-aryl or —NH—C(═O)—CH₂-heteroaryl; (iv) —NH—C(═Z)—NH—R¹⁵ preferably —NH—C(═O)—NH-alkyl, —NH—C(═O)—NH-aryl or —NH—C(═O)—NH-heteroaryl; (v) NH—C(═Z)—NH—L⁴—R¹⁶ preferably —NH—C(═O)—NH—CH₂-alkyl, —NH—C(═O)—NH—CH₂aryl or —NH—C(═O)—NH—CH₂heteroaryl; (vi) —NY⁴Y⁵, preferably —NH₂; (vii) aryl; (viii) heteroaryl; (ix) —N(R¹⁰)—SO₂—R¹⁵, preferably —NH—SO₂-alkyl, NH—SO₂-aryl or —NH—SO₂-heteroaryl} and R⁵ represents hydrogen, C₁₋₄alkyl (e.g. methyl) or hydroxyC₁₋₄alkyl (e.g. hydroxymethyl), especially methyl and R¹⁸ represents —NY⁴Y⁵ {where Y⁴ and Y⁵ are as hereinbefore defined, especially where Y⁴ is hydrogen and Y⁵ is (i) arylalkyl, particularly benzyl or α-methylbenzyl; (ii) heteroarylalkyl, particularly azaheteroarylalkyl, more particularly azaheteroaryl-CH₂; (iii) C₂₋₆alkyl substituted by alkoxy, particularly C₂₋₆alkyl substituted by methoxy; (iv) C₂₋₆alkyl substituted by —NY¹Y², particularly C₂₋₆alkyl substituted by —NMe₂; (v) C₂₋₆alkyl substituted by hydroxy; or (vi) cycloalkyl} or —OR¹⁷, where R¹⁷ is alkyl or cycloalkyl; and N-oxides thereof, and their prodrugs; and pharmaceutically acceptable salts and solvates (e.g. hydrates) of compounds of formula (Ia) herein and N-oxides thereof, and their prodrugs.

A particular groups of compounds of the invention are those selected from the following:

-   {2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     cis-isomer, (Compound A); -   {2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     transisomer, (Compound B); -   4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-1H-imidazol-4-yl]-pyridine,     (Compound C); -   C-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-methylamine,     cis- and trans-isomers (Compound D); -   2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-acetamide,     cis- and trans-isomers, (Compound E); -   2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-acetamide,     cis-isomer, (Compound F); -   2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]acetamide,     trans-isomer, (Compound G); -   4-[2-(5-azidomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-1H-imidazol-4-yl]-pyridine,     cis- and trans-isomers, (Compound H); -   4-[2-(5-benzyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-1H-imidazol-4-yl]-pyridine,     cis- and trans-isomers, (Compound I); -   2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid methyl ester, cis- and trans-isomers, (Compound J); -   4-[5-(4-fluoro-phenyl)-2-(1,8,10-trioxa-spiro[5.5]undec-9-yl)-1H-imidazol-4-yl]pyridine,     (Compound K); -   4-[5-(4-fluoro-phenyl)-2-(1,7,9-trioxa-spiro[4.5]dec-8-yl)-1H-imidazol-4-yl]-pyridine,     (Compound L); -   4-[2-(5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine,     (Compound M); -   4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyridine,     (Compound N); -   4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine,     (Compound O); -   4-[5-(4-fluoro-phenyl)-2-(4-methyl-[1,3-dioxan-2-yl)-3H-imidazol-4-yl]-pyridine,     (R/S)(R/S) isomers, (Compound P); -   4-[2-(4,6-dimethyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine,     (R/S)(R/S)(R/S) isomers, (Compound Q); -   4-[2-(5-benzyloxy-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine,     cis- and trans-isomers, (Compound R); -   4-[5-(4-fluoro-phenyl)-2-(5-phenyl-[1,3]dioxan-2yl)-3H-imidazol-4-yl]-pyridine,     cis- and trans-isomers, Compound S); -   4-[5-(4-fluoro-phenyl)-2-(4-isopropyl-5,5-dimethyl-[1,3]dioxan-2-yl)-3H-imidazol-4yl]-pyridine,     (R/S)(R/S) isomers, (Compound T); -   4-[2-(5,5-diethyl-[1,3]dioxan-2yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine,     (Compound U); -   4-[2-(2,4-dioxa-spiro[5.5]undec-8-en-3-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine,     cis- and trans-isomers, (Compound V); -   N-[2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl]-benzamide,     cis- and trans-isomers, (Compound W); -   1-(4-fluoro-phenyl)-3-[2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl]-thiourea,     cis- and trans-isomers (Compound X); -   1-(2,6-dimethyl-phenyl)-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-thiourea,     cis- and trans-isomers, Compound Y); -   4-[5-(4-fluoro-phenyl)-2-(5-methyl-5-pyrrol-1-yl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyridine,     cis- and trans-isomer, (Compound Z); -   C-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-methylamine,     trans-isomer, (Compound AA); -   C-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-methylamine     cis-isomer, (Compound AB); -   2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylmethyl]-acetamide,     trans-isomer, (Compound AC); -   2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylmethyl]-acetamide,     cis-isomer, (Compound AD); -   5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine,     cis-isomer, (Compound AE); -   5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine,     trans-isomer, (Compound AF); -   5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine,     cis- and trans-isomers, (Compound AG); -   2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid, trans-isomer, (Compound AH); -   2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid, cis-isomer, (Compound AI); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, cis-isomer, (Compound AJ); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound AK); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound AL); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound AM); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid amide, trans-isomer (Compound AN); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (pyridin-2-ylmethyl)-amide, trans-isomer, (Compound AO); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (pyridin-3-ylmethyl)-amide, trans-isomer, (Compound AP); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (pyridin-4-ylmethyl)-amide, trans-isomer, (Compound AQ); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound AR); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]-dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound AS); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]-dioxane-5-carboxylic     acid [2-(1H-indol-3-yl)-ethyl]-amide, trans-isomer, (Compound AT); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound AU); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-yl-methyl)-amide, trans-isomer, (Compound     AV); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound AW); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-pyrrolidin-1yl-methanone,     trans-isomer, (Compound AX); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid butylamide, trans-isomer, (Compound AY); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid dipropylamide, trans-isomer, (Compound AZ); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound BA); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenethyl-amide, trans-isomer (Compound BB); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-pyridin-2-yl-ethyl)-amide, trans-isomer, (Compound BC); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (furan-2-ylmethyl)amide, trans-isomer, (Compound BD); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}morpholin-4-yl-methanone,     trans-isomer, (Compound BE); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid dimethylamide, trans-isomer, (Compound BF); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound BG); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylamide, trans-isomer, Compound BH); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopentylamide, trans-isomer (Compound BI); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound BJ); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, cis-isomer, (Compound BK); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, cis-isomer, (Compound BL); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid amide, cis-isomer (Compound BM); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (pyridin-2-ylmethyl)-amide, cis-isomer, (Compound BN); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (pyridin-3-ylmethyl)-amide, cis-isomer, (Compound BO); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (pyridin-4-ylmethyl)-amide, cis-isomer, (Compound BP); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-yl}-morpholin-4-yl-methanone,     cis-isomer (Compound BQ); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5yl}-(4-methyl-piperazin-1yl)-methanone,     cis-isomer, (Compound BR); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, cis-isomer (Compound BS); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid [2-(1H-indol-3-yl)-ethyl]-amide, cis-isomer (Compound BT); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, cis-isomer, (Compound BU); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenethyl-amide, cis-isomer (Compound BV); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, cis-isomer, (Compound BW); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-pyridin-2-yl-ethyl)-amide, cis-isomer, (Compound BX); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (furan-2-ylmethyl)-amide, cis-isomer, (Compound BY); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, cis-isomer (Compound BZ); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-yl}-pyrrolidin-1-yl-methanone,     cis-isomer (Compound CA); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-yl}-piperidin-1-yl-methanone,     cis-isomer, (Compound CB); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, cis-isomer (Compound CC); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid butylamide, cis-isomer, (Compound CD); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylamide, cis-isomer (Compound CE); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopentylamide, cis-isomer Compound CF); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, cis-isomer (Compound CG); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid methylamide, cis-isomer, (Compound CH); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, cis-isomer, (Compound CI); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid dimethylamide, cis-isomer (Compound CJ); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid dipropylamide, cis-isomer, (Compound CK); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid ethylamide, cis-isomer, (Compound CL); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid methylamide, trans-isomer, (Compound CM); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid dimethylamino-ethyl)-amide, trans-isomer, (Compound CN); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid ethylamide, trans-isomer, (Compound CO); -   1-{2-[-4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-3-phenyl-urea,     cis-isomer, (Compound CP); -   1-ethyl-3-{2-[-4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-urea,     cis-isomer, (Compound CQ); -   1-(3,5-dimethyl-isoxazol-4-yl)-3-{2-[-4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-urea,     cis-isomer, (Compound CR); -   1-benzyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-urea,     cis-isomer, (Compound CS); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-3-(2-thiophen-2-yl-ethyl)-urea,     cis-isomer, (Compound CT); -   1-(3-acetyl-phenyl)-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-urea,     cis-isomer, (Compound CU); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-1,3]dioxan-5-yl}-3-phenyl-urea,     trans-isomer, (Compound CV); -   3-(3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-ureido)-benzoic     acid, trans-isomer, (Compound CW); -   1-benzyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-urea,     trans-isomer, (Compound CX); -   1-ethyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-urea,     trans-isomer, (Compound CY); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-3-(2-thiophen-2-yl-ethyl)-urea,     trans-isomer, (Compound CZ); -   1-benzyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-urea,     cis-isomer, (Compound DA); -   1-ethyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl}-urea,     cis-isomer, (Compound DB); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-phenyl-urea,     cis-isomer, (Compound DC); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-phenyl-urea,     trans-isomer, (Compound DD); -   1-benzyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-urea,     trans-isomer, (Compound DE); -   1-ethyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-urea,     trans-isomer, (Compound DF); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-3-(2-morpholin-4-yl-ethyl)-thiourea,     cis-isomer, (Compound DG); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-3-furan-3-ylmethyl-thiourea,     cis-isomer, (Compound DH); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-3-pyridin-3-yl-thiourea,     cis-isomer, (Compound DI); -   1-benzo[1,3]dioxol-5-yl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-thiourea,     cis-isomer, (Compound DJ); -   1-benzo[1,3]dioxol-5-ylmethyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-thiourea,     cis-isomer, (Compound DK); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-pyridin-3-yl-thiourea,     trans-isomer, (Compound DL); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-(2-morpholin-4-yl-ethyl)-thiourea,     trans-isomer, (Compound DM); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-furan-2-ylmethyl-thiourea,     trans-isomer, (Compound DN); -   1-benzo[1,3]dioxol-5-ylmethyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-thiourea,     trans-isomer, (Compound DO); -   1-benzo[1,3]dioxol-5-yl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-thiourea,     cis-isomer, (Compound DP); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-furan-2-ylmethyl-thiourea,     cis-isomer, (Compound DQ); -   3-(3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-thioureido)-benzoic     acid, cis-isomer, (Compound DR); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-pyridin-3-yl-thiourea,     cis-isomer, (Compound DS); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-(2-morpholin-4-yl-ethyl)-thiourea,     cis-isomer, (Compound DT); -   1-benzo[1,3]dioxol-5-ylmethyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-thiourea,     cis-isomer, (Compound DU); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide,     cis-isomer, (Compound DV); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-phenyl-acetamide,     cis-isomer, (Compound DW); -   cyclohexanecarboxylic acid     {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-amide,     cis-isomer, (Compound DX); -   2-benzyloxy-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide,     trans-isomer, (Compound DY); -   2-benzyloxy-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide,     cis-isomer, (Compound DZ); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide,     trans-isomer, (Compound EA); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-2-phenyl-acetamide,     trans-isomer, (Compound EB); -   cyclohexanecarboxylic acid     {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-amide,     trans-isomer (Compound EC); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-2-phenyl-acetamide,     cis-isomer, (Compound ED); -   2-benzyloxy-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound EE); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound EF); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound EG); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound EH); -   cyclohexanecarboxylic acid     {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-amide,     cis-isomer, (Compound EI); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     trans-isomer, (Compound EJ); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     trans-isomer, (Compound EK); -   cyclohexanecarboxylic acid     {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-amide,     trans-isomer, (Compound EL); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     trans-isomer, (Compound EM); -   4-{2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-butyric     acid, cis-isomer, (Compound EN); -   4-({2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-carbamoyl)-butyric     acid, cis-isomer, (Compound EO); -   4-{2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-propionic     acid, cis-isomer, (Compound EP); -   4-({2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-carbamoyl)-propionic     acid, cis-isomer, (Compound EQ); -   4-({2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-carbamoyl)-propionic     acid, trans-isomer, (Compound ER); -   N-{2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanesulphonamide,     cis-isomer, (Compound ES); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulphonamide,     cis-isomer, (Compound ET); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzenesulphonamide,     cis-isomer, (Compound EU); -   N-{2-[5-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-C-phenyl-methanesulphonamide,     cis-isomer, (Compound EV); -   thiophene-2-sulphonic acid     {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-amide,     cis-isomer, (Compound EW); -   3,5-dimethyl-isoxazole-4-sulphonic acid     {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl]-amide,     cis-isomer, (Compound EX); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulphonamide,     trans-isomer, (Compound EY); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzenesulphonamide,     trans-isomer, (Compound EZ); -   thiophene-2-sulphonic acid     {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-amide,     trans-isomer, (Compound FA); -   3,5-dimethyl-isoxazole-4-sulphonic acid     {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl]-amide,     trans-isomer, (Compound FB); -   3-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-propionamide,     trans-isomer, (Compound FC); -   3-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-propionamide,     cis-isomer, (Compound FD); -   4-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-butyramide,     trans-isomer, (Compound FE); -   4-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-butyramide,     cis-isomer, (Compound FF); -   2-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide,     trans-isomer, (Compound FG); -   2-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide,     cis-isomer, (Compound FH); -   (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-ethyl)-carbamic     acid benzyl ester, trans-isomer, (Compound FI); -   (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-ethyl)-carbamic     acid benzyl ester, cis-isomer, (Compound FJ); -   (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-propyl)-carbamic     acid benzyl ester, trans-isomer, (Compound FK); -   (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-propyl)-carbamic     acid benzyl ester, cis-isomer, (Compound FL); -   (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-methyl)-carbamic     acid benzyl ester, trans-isomer, (Compound FM); -   (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-methyl)-carbamic     acid benzyl ester, cis-isomer, (Compound FN); -   4-dimethylamino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-butyramide,     cis- and trans-isomers, (Compound FO); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-benzamide,     trans-isomer, (Compound FR); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-hydroxy-piperidin-1-yl)-methanone,     trans isomer, (Compound FS); -   (1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanone,     trans isomer, (Compound FT); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carbonyl}-piperidine-4-carboxylic     acid ethyl ester, trans isomer, (Compound FU); -   1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carbonyl}-piperidine-4-carboxylic     acid, trans isomer, (Compound FV); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-thiomorpholin-4-yl-methanone,     trans isomer, (Compound FW); -   (1,1-dioxothiomorpholin-4-yl)-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanone,     trans isomer, (Compound FX); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxymethyl-piperidin-1-yl)-methanone,     trans isomer, (Compound FY); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-piperidin-1-yl)-methanone,     trans isomer, (Compound FZ); -   (2,6-dimethyl-morpholin-4-yl)-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanone,     trans isomer, (Compound GA); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans isomer, (Compound GB); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methoxy-piperidin-1-yl)-methanone,     trans isomer, (Compound GC); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-[4-(2-hydroxy-ethyl)-piperidin-1-yl]-methanone,     trans isomer, (Compound GD); -   {5-Amino-2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-[1,3]-5-yl}-methanol,     cis isomer, (Compound LE); -   {5-Amino-2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-[1,3]-5-yl}-methanol,     trans isomer, (Compound LF); -   {2-[4-(4-Fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-nitro-[1,3]dioxan-5-yl}-methanol,     cis isomer, (Compound LG); -   {2-[4-(4-Fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-nitro-[1,3]dioxan-5-yl}-methanol,     trans isomer, (Compound LH); -   C-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5,5-dimethyl-[1,3]dioxan-4-yl}-methylamine     (Compound LI); -   4-[2-(5,5-dimethyl-4-nitromethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine     (Compound LJ); and the corresponding N-oxides, and their prodrugs;     and pharmaceutically acceptable salts and solvates (e.g. hydrates)     of such compounds and their N-oxides and prodrugs.

A further particular group of compounds of the invention are those selected from the following:

-   {2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans isomer, (Compound GE); -   2-[5-(2-Amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound GI); -   {2-[5-(2-Dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound GJ); -   (2-{4-(4-Fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound GK); -   (2-{4-(4-Fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound GL); -   {2-[4-(4-Fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer (Compound GM); -   (2-{4-(4-Fluoro-phenyl)-5-[2-(1-ethoxycarbonylpiperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound GN); -   {2-[5-(2-Cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound GO); -   (2-{4-(4-Fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound GP); -   {2-[5-[2-(2-Amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound GQ); -   [2-(4-(4-Fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer (Compound GR); -   (2-{4-(4-Fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound GS); -   2-[5-(2-Benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound GT); -   (2-{4-(4-Fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     R isomer, trans-isomer, (Compound GU); -   (2-{4-(4-Fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     S isomer, trans-isomer, (Compound GV); -   {2-[4-(4-Fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound GW); -   {2-[4-(4-Fluoro-phenyl)-5-(2-piperidinyl-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound GX); -   [2-(4-(4-Fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound GY); -   [2-(4-(4-Fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound GZ); -   [2-(4-(4-Fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound HA); -   [2-(4-(4-Fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound HB); -   [2-(4-(4-Fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound HC); -   [2-(4-(4-Fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound HD); -   (2-{4-(4-Fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound HE); -   {2-[4-(4-Fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound HF); -   (2-{4-(4-Fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound FG); -   {2-[5-[2-(3-Dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound HH); -   {2-[5-[2-(2-Dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound HI); -   (4-{5-(4-Fluoro-phenyl)-2-[5-methyl-5-(morpholine-4-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetic     acid, trans-isomer, (Compound HJ); -   3-(4-{5-(4-Fluoro-phenyl)-2-[5-methyl-5-(morpholine-4-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionic     acid, trans-isomer, (Compound HK); -   4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamine,     (Compound HL); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-methyl-amine,     (Compound HM); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-dimethyl-amine,     (Compound HN); -   cyclopropyl-{4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,     (Compound HO); -   cyclohexyl-{4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,     (Compound HQ); -   2-{4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-ethanol,     (Compound HR); -   N1-{4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-ethane-1,2-diamine,     (Compound HS); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-[3-(5H-imidazol-1-yl)-propyl]-amine,     (Compound HT); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-[3-morpholin-4-yl-propyl)-amine,     (Compound HU); -   3-{4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propan-1-ol,     (Compound HV); -   benzyl-{4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,     (Compound HW); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-(1-phenyl-ethyl)-amine,     R-isomer, (HX); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(1-phenyl-ethyl)-amine,     S-isomer, (HY); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-phenyl-amine,     (HZ); -   4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-piperidin-1-yl-pyrimidine,     (Compound IA); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-4-ylmethyl-amine,     (Compound IB); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-2-ylmethyl-amine,     (Compound IC); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-3-ylmethyl-amine,     (Compound ID); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-furan-2-ylmethyl)-amine,     (Compound IE); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(thiophen-2-ylmethyl)-amine,     (Compound IF); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(tetrahydro-furan-2-ylmethyl)-amine,     (Compound IG); -   4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-(4-methyl-piperazin-1-yl)-pyrimidine,     (Compound IH); -   4-[4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-morpholine,     (Compound IJ); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(3-methoxy-propyl)-amine,     (Compound IK); -   {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(2-methoxy-ethyl)-amine,     (Compound IL); -   N-{4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-N′,N′-dimethyl-propane-1,3-diamine,     (Compound IM); -   N-{4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-N′,N′-dimethyl-ethane-1,2-diamine,     (Compound IN); -   {2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound IO) -   {2-[4-(4-Fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound IP); -   {2-[5-(2-Benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound IQ); -   {2-[4-(4-Fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound IR); -   (2-{4-(4-Fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound IS); -   {2-[5-[2-(2-Dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound IT); -   {2-[5-(2-Cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound IU); -   {2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound IW); -   4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-methoxy-pyrimidine,     (Compound IY); -   2-benzyloxy-4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidine,     (Compound IZ); -   4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-phenoxy-pyrimidine,     (Compound JA); -   4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-(2-methoxy-ethoxy)-pyrimidine,     (Compound JB); -   (2-{4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimdin-2-yloxy}-ethyl)-dimethyl-amine,     (Compound JC); -   2-cyclohexyloxy-4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidine,     (Compound JD); -   2-isopropoxy-4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidine,     (Compound JE); -   4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamine,     cis-isomer, (Compound JF); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-methyl-amine,     cis-isomer, (Compound JG); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-dimethyl-amine,     cis-isomer, (Compound JH); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-cyclopropyl-amine,     cis-isomer, (Compound JI); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-piperidin-4-yl-amine,     cis-isomer, (Compound JJ); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-cyclohexyl-amine,     cis-isomer, (Compound JK); -   2-{4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-ethanol     cis-isomer, (Compound JL); -   N1-{4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-ethane-1,2-diamine,     cis-isomer, (Compound JM); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-[3-(5H-imidazol-1-yl)-propyl]-amine,     cis-isomer, (Compound JN); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-[3-morpholin-4-yl-propyl)-amine,     cis-isomer, (Compound JO); -   3-{4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propan-1-ol,     cis-isomer, (Compound JP); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-benzyl-amine,     cis-isomer, (Compound JQ); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(1-phenyl-ethyl)-amine,     R isomer, cis-isomer, (Compound JR); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(1-phenyl-ethyl)-amine,     S isomer, cis-isomer, (Compound JS); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-phenyl-amine,     cis-isomer, (Compound JT); -   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylamine,     cis-isomer, (Compound JU); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-4-ylmethyl-amine,     cis-isomer, (Compound JV); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-2-ylmethyl-amine,     cis-isomer, (Compound JW); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-3-ylmethyl-amine,     cis-isomer, (Compound JX); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(furan-2-ymethyl)-amine,     cis-isomer, (Compound JY); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(thiophen-2-ylmethyl)-amine,     cis-isomer, (Compound JZ); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(tetrahydro-furan-2-ylmethyl)-amine,     cis-isomer, (Compound KA); -   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylamine,     cis-isomer, (Compound KB); -   2-{4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylamine,     cis-isomer, (Compound KC); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(3-methoxy-propyl)-amine,     cis-isomer, (Compound KD); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(2-methoxy-ethyl)-amine,     cis-isomer, (Compound KE); -   N-{4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-N′,N′-dimethyl-propane-1,3-diamine,     cis-isomer, (Compound KF); -   N-{4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-N′,N′-dimethyl-ethane-1,2-diamine,     cis-isomer, (Compound KG); -   {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans isomer, (Compound KH); -   2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5,5-dimethyl-[1,3]dioxane     (Compound KI); -   {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound KJ); -   {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     cis-isomer, (Compound KK); -   2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methylene-[1,3]dioxane     (Compound KL). -   4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-methylsulphonyl-pyrimidine     (Compound KM); -   {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,     trans-isomer (Compound KN); -   {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,     cis-isomer (Compound KO); -   2,2,2-trifluoro-N-[2-{4-(4-fluoro-phenyl)-5-(2-methanesulphonylpyrimidin-4-yl)-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl]acetamide,     cis-isomer (Compound KP); -   {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans isomer, (Compound KQ); -   2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanylpyrimidin-4-yl)-1H-imidazol-2-yl]-5,5-dimethyl-[1,3]dioxane     (Compound KR); -   2,2,2-trifluoro-N-[2-{4-(4-fluoro-phenyl)-5-(2-methanesulphanyl-pyrimidin-4-yl)-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl]acetamide,     cis-isomer (Compound KS); -   {2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     cis isomer (Compound KT); -   {2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     trans isomer (Compound KU); -   4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-2-methylsulfanyl-pyrimidine     (Compound KV); -   4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-methylsulphanyl-pyrimidine     (Compound KW); -   {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,     trans-isomer (Compound KX); -   {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,     cis-isomer (Compound KY); -   C-{2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methylamine,     cis isomer (Compound KZ); -   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid amide, cis isomer Compound LA); -   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid, cis isomer (Compound LB); -   2-[4-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-carboxylic     acid methyl ester, trans isomer (Compound LC); -   2-[4-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid methyl ester, cis isomer (Compound LD); -   2,2,2-trifluoro-N-{2-[5-(2-methylsulphonyl-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis isomer, (Compound LK); -   2,2,2-trifluoro-N-{2-[5-(2-methylsulphonyl-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     trans isomer, (Compound LL); -   2-[4-(4-fluorophenyl)-5-(2-methylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-carboxylic     acid methyl ester, trans isomer (Compound LM); -   2-[4-(4-fluorophenyl)-5-(2-methylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-carboxylic     acid methyl ester, cis isomer (Compound LN); and the corresponding     N-oxides, and their prodrugs; and pharmaceutically acceptable salts     and solvates (e.g. hydrates) of such compounds and their N-oxides     and prodrugs.

Preferred compounds of the invention include:

-   {2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     cis-isomer, (Compound A); -   C-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-methylamine,     cis- and trans-isomers, (Compound D); -   4-[5-(4-fluoro-phenyl)-2-(4-isopropyl-5,5-dimethyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyridine,     (R/S)(R/S) isomers, (Compound T); -   C-[5-methyl-2-(5-phenyl-4-pyridin-4-yl-1H-imidazol-2-yl)-[1,3]dioxan-5-yl]-methylamine,     trans-isomers, (Compound AA); -   C-[5-methyl-2-(5-phenyl-4-pyridin-4-yl-1H-imidazol-2-yl)-[1,3]dioxan-5-yl]-methylamine,     cis-isomer, (Compound AB); -   5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine,     cis-isomer, (Compound AE); -   5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine,     trans-isomer, (Compound AF); -   5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine,     cis- and trans-isomers, (Compound AG); -   2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid amide, trans-isomer, (Compound AN); -   {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     cis-isomer, (Compound BM); -   amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide,     trans-isomer, (Compound FC); -   amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide,     cis-isomer, (Compound FD); -   N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-benzamide,     trans-isomer, (Compound FR); and the corresponding N-oxides, and     their prodrugs; and pharmaceutically acceptable salts and solvates     (e.g. hydrates) of such compounds and their N-oxides and prodrugs.

Further preferred compounds of the invention include:

-   {2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans isomer, (Compound GE); -   (2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans isomer, (Compound GI); -   2-{4-(4-fluoro-phenyl)-5-[2-(1-ethoxycarbonylpiperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans isomer, (Compound GK); -   {2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans isomer, (Compound GL); -   and the corresponding N-oxides, and their prodrugs; and     pharmaceutically acceptable salts and solvates (e.g. hydrates) of     such compounds and their N-oxides and prodrugs.

A particularly preferred compound of the invention is {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, trans-isomer, (Compound AW); and the corresponding N-oxide, and its prodrugs; and pharmaceutically acceptable salts and solvates (e.g. hydrates) of this compound and its N-oxide and prodrugs, especially its methane sulphonic acid salt as depicted by Compound FP.

The compounds of the invention exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. The present invention thus provides, according to a further aspect, compounds of the invention and compositions containing compounds of the invention for use in therapy.

Compounds within the scope of the present invention are inhibitors of the generation of tumour necrosis factor (TNF), especially TNF-alpha, according to tests described in the literature and described in vitro and in vivo procedures hereinafter, and which tests results are believed to correlate to pharmacological activity in humans and other mammals. Thus, in a further embodiment, the present invention provides compounds of the invention and compositions containing compounds of the invention for use in the treatment of a patient suffering from, or subject to, conditions which can be ameliorated by the administration of an inhibitor of TNF, especially of TNF-alpha. For example, compounds of the present invention are useful in the treatment of joint inflammation, including arthritis, rheumatoid arthritis and other arthritic conditions such as rheumatoid spondylitis, gouty arthritis, traumatic arthritis, rubella arthritis, psoriatic arthritis and osteoarthritis. Additionally, the compounds are useful in the treatment of acute synovitis, tuberculosis, atherosclerosis, muscle degeneration, cachexia, Reiter's syndrome, endotoxaemia, sepsis, septic shock, endotoxic shock, gram negative sepsis, gout, toxic shock syndrome, chronic pulmonary inflammatory diseases including asthma and adult respiratory distress syndrome, silicosis, pulmonary sarcoidosis, bone resorption diseases, osteoporosis, restenosis, heart failure and myocardial ischaemic syndromes, cardiac and renal reperfusion injury, thrombosis, glomerularnephritis, graft vs. host reaction, allograft rejection and leprosy. Furthermore, the compounds are useful in the treatment of infections such as viral infections, for example HIV, cytomegalovirus (CMV), influenza, adenovirus and the Herpes group of viruses, parasitic infections, for example malaria such as cerebral malaria, and yeast and fungal infections, for example fungal meningitis; fever and myalgias due to infection; AIDS; AIDS related complex (ARC); cachexia secondary to infection or malignancy; cachexia secondary to acquired immune deficiency syndrome (AIDS) or to cancer; keloid and scar tissue formation; pyresis; diabetes; inflammatory bowel diseases such as Crohn's disease and ulcerative colitis; eczema; contact dermititis; psoriasis; sunburn and conjunctivitis.

Compounds of the invention are also useful in the treatment of diseases of, or injury to, the brain in which over-production of TNF-alpha has been implicated, such as multiple sclerosis, Alzheimers disease, trauma, stroke and other ischaemic conditions.

Compounds of the invention may also be useful in inhibiting diseases associated with over-production of other pro-inflammatory cytokines, IL-1, IL-6 and IL-8.

A special embodiment of the therapeutic methods of the present invention is the treating of asthma.

Another special embodiment of the therapeutic methods of the present invention is the treating of joint inflammation.

According to a further feature of the invention there is provided a method for the treatment of a human or animal patient suffering from, or subject to, conditions which can be ameliorated by the administration of an inhibitor of TNF, especially TNF-alpha, for example conditions as hereinbefore described, which comprises the administration to the patient of an effective amount of compound of the invention or a composition containing a compound of the invention. “Effective amount” is meant to describe an amount of compound of the present invention effective in inhibiting TNF and thus producing the desired therapeutic effect.

References herein to treatment should be understood to include prophylactic therapy as well as treatment of established conditions.

The present invention also includes within its scope pharmaceutical compositions comprising at least one of the compounds of the invention in association with a pharmaceutically acceptable carrier or excipient.

Compounds of the invention may be administered by any suitable means. In practice compounds of the present invention may generally be administered parenterally, topically, rectally, orally or by inhalation, especially by the oral route.

Compositions according to the invention may be prepared according to the customary methods, using one or more pharmaceutically acceptable adjuvants or excipients. The adjuvants comprise, inter alia, diluents, sterile aqueous media and the various non-toxic organic solvents. The compositions may be presented in the form of tablets, pills, granules, powders, aqueous solutions or suspensions, injectable solutions, elixirs or syrups, and can contain one or more agents chosen from the group comprising sweeteners, flavorings, colorings, or stabilizers in order to obtain pharmaceutically acceptable preparations. The choice of vehicle and the content of active substance in the vehicle are generally determined in accordance with the solubility and chemical properties of the active compound, the particular mode of administration and the provisions to be observed in pharmaceutical practice. For example, excipients such as lactose, sodium citrate, calcium carbonate, dicalcium phosphate and disintegrating agents such as starch, alginic acids and certain complex silicates combined with lubricants such as magnesium stearate, sodium lauryl sulphate and talc may be used for preparing tablets. To prepare a capsule, it is advantageous to use lactose and high molecular weight polyethylene glycols. When aqueous suspensions are used they can contain emulsifying agents or agents which facilitate suspension. Diluents such as sucrose, ethanol, polyethylene glycol, propylene glycol, glycerol and chloroform or mixtures thereof may also be used.

For parenteral administration, emulsions, suspensions or solutions of the products according to the invention in vegetable oil, for example sesame oil, groundnut oil or olive oil, or aqueous-organic solutions such as water and propylene glycol, injectable organic esters such as ethyl oleate, as well as sterile aqueous solutions of the pharmaceutically acceptable salts, are used. The solutions of the salts of the products according to the invention are especially useful for administration by intramuscular or subcutaneous injection. The aqueous solutions, also comprising solutions of the salts in pure distilled water, may be used for intravenous administration with the proviso that their pH is suitably adjusted, that they are judiciously buffered and rendered isotonic with a sufficient quantity of glucose or sodium chloride and that they are sterilized by heating, irradiation or microfiltration.

For topical administration, gels (water or alcohol based), creams or ointments containing compounds of the invention may be used. Compounds of the invention may also be incorporated in a gel or matrix base for application in a patch, which would allow a controlled release of compound through the transdermal barrier.

For administration by inhalation compounds of the invention may be dissolved or suspended in a suitable carrier for use in a nebulizer or a suspension or solution aerosol, or may be absorbed or adsorbed onto a suitable solid carrier for use in a dry powder inhaler.

Solid compositions for rectal administration include suppositories formulated in accordance with known methods and containing at least one compound of the invention.

The percentage of active ingredient in the compositions of the invention may be varied, it being necessary that it should constitute a proportion such that a suitable dosage shall be obtained.

Obviously, several unit dosage forms may be administered at about the same time. The dose employed will be determined by the physical, and depends upon the desired therapeutic effect, the route of administration and the duration of the treatment, and the condition of the patient. In the adult, the doses are generally from about 0.001 to about 50, preferably about 0.001 to about 5, mg/kg body weight per day by inhalation, from about 0.01 to about 100, preferably 0.1 to 70, more especially 0.5 to 10, mg/kg body weight per day by oral administration, and from about 0.001 to about 10, preferably 0.01 to 1, mg/kg body weight per day by intravenous administration. In each particular case, the doses will be determined in accordance with the factors distinctive to the subject to be treated, such as age, weight, general state of health and other characteristics which can influence the efficacy of the medicinal product.

The compounds according to the invention may be administered as frequently as necessary in order to obtain the desired therapeutic effect. Some patients may respond rapidly to a higher or lower dose and may find much weaker maintenance doses adequate. For other patients, it may be necessary to have long-term treatments at the rate of 1 to 4 doses per day, in accordance with the physiological requirements of each particular patient. Generally, the active product may be administered orally 1 to 4 times per day. Of course, for some patients, it will be necessary to prescribe not more than one or two doses per day.

Compounds of the invention may be prepared by the application or adaptation of known methods, by which is meant methods used heretofore or described in the literature.

Compounds of the invention may be prepared by methods similar to those described in EP424195 and EP506437.

In the reactions described hereinafter it may be necessary to protect reactive functional groups, for example hydroxy, amino, imini, thio or carboxy groups, where these are desired in the final product, to avoid their unwanted participation in the reactions. Conventional protecting groups may be used in accordance with standard practice, for examples see T. W. Greene and P. G. W. Wuts in “Protective Groups in Organic Chemistry” John Wiley and Sons, 1991.

Compounds of this invention may be represented by the formula (Ic):

wherein R⁴, R⁵, R⁶ and m are as hereinbefore defined and T¹ represents a group of the formula:

wherein R¹, R² and R³ are as hereinbefore defined.

In a process (A), compounds of formula (I), wherein R¹, R², R⁴, R⁵, R⁶ and m are as hereinbefore defined and R³ is hydrogen, may be prepared by reaction of compounds of formula (II):

wherein R¹ and R² are as hereinbefore defined, R¹⁹ is hydrogen or a suitable protecting group, such as 2-trimethylsilanyl-ethoxymethyl, which is subsequently removed under the acidic reaction condition and R²⁰ is —CHO or —CH(OMe)₂, with compounds of formula (III):

wherein R⁴, R⁵, R⁶ and m are hereinbefore defined. The reaction may conveniently be carried out in the presence of an acid catalyst, such as pyridinium 4-toluene sulphonate or 4-toluene sulphonic acid, in an inert solvent, such as toluene, at reflux temperature, with azetropic removal of the water formed in the reaction.

Compounds of formula (I), wherein R¹, R², R⁴, R⁵, R⁶ and m are as hereinbefore defined and R³ represent a group —L¹—R⁷ (where L¹ and R⁷ are as hereinbefore defined) or —L²—R⁸ (where L² is as hereinbefore defined and R⁸ is aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocycloalkyl) may be similarly prepared by reaction of compounds of formula (II), wherein R¹, R²are as hereinbefore defined, R¹⁹ represents a group —L¹—R⁷ (where L¹ and R⁷ are as hereinbefore defined) or —L²—R⁸ (where L²is as hereinbefore defined and R⁸ is aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocycloalkyl) and R²⁰ is —CHO or —CH(OMe)₂), with compounds of formula (III) wherein R⁴, R⁵, R⁶ and m are as hereinbefore defined.

In a process B, compounds of formula (I), wherein R², R³, R⁴, R⁵, R⁶ and m are as hereinbefore defined, and R¹ represents a group (IV):

wherein R¹⁸ is Y⁴Y⁵N— (in which Y⁴ and Y⁵ are as hereinbefore defined), may be prepared by:

-   -   (i) treating Merrifield resin (chloromethylpolystyrene resin)         with potassium thioacetate in an inert solvent, such as         dimethylformamide, at a temperature at about room temperature,         to give Resin A;     -   (ii) reaction of Resin A with lithium borohydride in an inert         solvent, such as tetrahydrofuran, and at a temperature at about         room temperature, to give Resin B;     -   (iii) reaction of Resin B with an alkali metal hydride, such as         sodium hydride, in an inert solvent, such as dimethylformamide,         at a temperature at about room temperature, followed by         treatment with compounds of formula (V);     -    wherein R², R³, R⁴, R⁵, R⁶ and m are as hereinbefore defined,         at a temperature from about room temperature to about 80° C., to         give Resin C;     -    in which R², R³, R⁴, R⁵, R⁶ and m are as hereinbefore defined;         followed by appropriate functional group interconversions, for         example those described hereinafter.     -   (iv) reaction of Resin C, in which R², R³, R⁴, R⁵, R⁶ and m are         as hereinbefore defined, with m-chloroperoxybenzoic acid, in an         inert solvent or preferably in a mixture of inert solvents, such         as a mixture of dichloromethane and methanol, to give resin D,         in which R², R³, R⁴, R⁵, R⁶ and m are as hereinbefore defined;     -   (v) reaction of Resin D, wherein R², R³, R⁴, R⁵, R⁶ and m are as         hereinbefore defined, with amines of formula HNY⁴Y⁵, wherein Y⁴         and Y⁵ are as hereinbefore defined, in an inert solvent, such as         dimethoxyethane, and at a temperature at about 70° C.

Compounds of formula (I), wherein R², R³, R⁴, R⁵, R⁶ and m are as hereinbefore defined and R¹ represents a group (IV), wherein R¹⁸ is a —OR¹⁷ or —SR¹⁷ group (in which R¹⁷ is as hereinbefore defined), may be prepared by reaction of Resin D, wherein R², R³, R⁴, R⁵, R⁶ and m are as hereinbefore defined, with compounds of formula R¹⁷OH or R¹⁷SH (in which R¹⁷ is as hereinbefore defined), in the presence of an alkali metal hydride, such as sodium hydride, in an inert solvent, such as dimethylformamide, and at a temperature from about room temperature to about 80° C.

According to a further feature of the present invention, compounds of the invention may be prepared by interconversion of other compounds of the invention.

For example compounds of formula (I), wherein R¹, R², R⁴, R⁵, R⁶ and m are as hereinbefore defined and R³ is group —L¹—R⁷ (in which L¹ represents a straight- or branched-chain alkylene linkage containing from 1 to about 6 carbon atoms and R⁷ is as hereinbefore defined), may be prepared by alkylation of compounds of formula (I) wherein R¹, R², R⁴, R⁵, R⁶ and m are as hereinbefore defined and R³ is hydrogen, with an alkyl halide of formula (IV): X¹—L²—R⁷   (IV) wherein L¹ and R⁷ are as hereinbefore defined immediately above and X¹ is a halogen atom, preferably a bromine atom. The alkylation may for example be carried out in the presence of a base, such as an alkali metal hydride, e.g. sodium hydride, in dimethylformamide, or dimethyl sulphoxide, at a temperature from about 0° C. to about 100° C.

As another example of the interconversion process, compounds of formula (I), wherein R¹, R², R⁴, R⁵, R⁶ and m are as hereinbefore defined and R³ is a group —L²—R⁸ (in which L² represents a straight- or branched-carbon chain comprising from 2 to about 6 carbon atoms and contains a double or triple carbon-carbon bond, and R⁸ is aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocycloalkyl), may be similarly prepared by alkylation of compounds of formula (I), wherein R¹, R², R⁴, R⁵, R⁶ and m are as hereinbefore defined and R³ is hydrogen, with compounds of formula (V): X¹—L²—R⁸   (V) wherein L² and R⁸ are as hereinbefore defined immediately above and X¹ is a halogen atom, preferably a bromine atom.

As another example of the interconversion process, compounds of formula (Ic), wherein T¹, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —NH₂ group, may be prepared by reaction of compounds of formula (Ic) wherein T¹, R⁵, R⁶ and m are as hereinbefore defined, and R⁴ contains a —NHC(═O)CF₃ group, with a base such as potassium or ammonium carbonate in methanol, or a mixture of methanol and water, at a temperature at about reflux temperature.

As another example of the interconnection process, compounds of formula (Ic), wherein T¹, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —N(R¹⁰)—C(═O)—R¹⁵ or —N(R¹⁰)—C(═O)—L⁴—R¹⁶ group (in which R¹⁰, R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined), may be prepared by reaction of compounds of formula (Ic) wherein T¹, R⁵, R⁶ and m are as hereinbefore defined, and R⁴ contains a —NHR¹⁰ group (in which R¹⁰ is as hereinbefore defined), with the appropriately substituted acid chloride Cl—C(═O)—R¹⁵ or Cl—C(═O)—L⁴—R¹⁶ (in which R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined) in the presence of triethylamine in an inert solvent such as tetrahydrofuran and at a temperature at about room temperature.

As another example of the interconversion process, compounds of formula (Ic), wherein T¹, R⁵, R⁶ and m are as hereinbefore defined, and R⁴ contains a —NH—C(═O)—R¹⁵ or —NH—C(═O)—L⁴—R¹⁶ group (in which R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined), may be prepared by reaction of compounds of formula (Ic), wherein T¹, R⁵, R⁶ and m are as hereinbefore defined, and R⁴ contains a —NH₂ group, with the appropriately substituted HO—C(═O)—R¹⁵ or HO—C(═O)—L⁴—R¹⁶ (in which R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined) respectively, in the presence of O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate and diisopropylethylamine in dimethylformamide, at room temperature. Other standard peptide coupling procedures may be employed for the reaction, such as treatment with a carbodiimide, for example dicyclohexylcarbodiimide, in the presence of triethylamine, or treatment with 1-hydroxybenzotriazole and a carbodiimide, such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, in an inert solvent such as dimethylformamide and at a temperature at about room temperature.

As another example of the interconversion process, compounds of formula (Ic), wherein R¹, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —NH—C(═O)—R¹⁵ or a —NH—C(═O)—L⁴—R¹⁶ group (in which R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined), may be prepared by reaction of compounds of formula (Ic), wherein T¹, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —NH₂ group, with the appropriately substituted acid anhydride R¹⁵—C(═O)—O—C(═O)—R¹⁵ or R¹⁶—L⁴—C(═O)—O—C(═O)—L⁴—R¹⁶ (in which R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined) in the presence of triethylamine or pyridine, in an inert solvent, such as tetrahydrofuran, and at a temperature at about room temperature.

As another example of the interconversion process, compounds of formula (Ic), wherein T¹, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —NH—C(═O)—NH—R¹⁵ or —NH—C(═O)—NH—L⁴—R¹⁶ group (in which R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined), may be prepared by reaction of compounds of formula (Ic) wherein T¹, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —NH₂ group, with the appropriately substituted isocyanate O═C═N—R¹⁵ or O═C═N—L⁴—R¹⁶ (in which R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined), in an inert solvent, such as tetrahydrofuran, and at a temperature at about room temperature.

As another example of the interconversion process, compounds of formula (Ic) wherein T¹, R⁵, R⁶ and m are as hereinbefore defined, and R⁴ contains a —NH—(C═S)—NH—R¹⁵ or —NH—(C═S)—NH—L⁴—R¹⁶ group (in which R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined), may prepared by reaction of compounds of formula (Ic) wherein T¹, R⁵, R⁶ and m are as defined, and R⁴ contains a —NH₂ group, with the appropriately substituted isothiocyanate S═C C═N—R¹⁵ or S═C═N—L⁴—R¹⁶ (in which R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined), in an inert solvent, such as tetrahydrofuran, and at a temperature at about reflux temperature.

As another example of the interconversion process, compounds of formula (Ic), wherein T¹, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —CO₂H group, may be prepared by hydrolysis of corresponding compounds of formula (Ic), wherein T¹, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —CO₂R²¹ group (in which R²¹ is as hereinbefore defined). The hydrolysis may conveniently be carried out by alkaline hydrolysis using a base, such as an alkali metal hydroxide or carbonate, in the presence of an aqueous/organic solvent mixture, using organic solvents such as dioxan, tetrahydrofuran or methanol, at a temperature from about ambient to about reflux. The hydrolysis may also be carried out by acid hydrolysis using an inorganic acid, such as hydrochloric acid, in the presence of an aqueous/inert organic solvent mixture, using organic solvents such as dioxan or tetrahydrofuran, at a temperature from about 50° C. to about 80° C.

As another example of the interconversion process, compounds of formula (Ic), wherein T¹, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —C(═O)—NY⁴Y⁵ group (in which Y⁴ and Y⁵ are as hereinbefore defined), may be prepared by reaction of compounds of formula (Ic), wherein T¹, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —CO₂H group, with an appropriately substituted amine of formula HNY⁴Y⁵ (in which Y⁴ and Y⁵ are as hereinbefore defined). The coupling reaction may conveniently be carried out in the presence of 1-hydroxybenzotriazole and a carbodiimide such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide in an inert solvent such as dimethylformamide and at a temperature at about room temperature. Alternatively the reaction may be carried out by initial conversion of the acid of formula (Ic), wherein R⁴ contains a —CO₂H group, to the corresponding acid chloride (for example by reaction with thionyl chloride or oxalyl chloride at room temperature) followed by treatment with an appropriately substituted amine of formula HNY⁴Y⁵.

As another example of the interconversion process, compounds of formula (I) containing sulphoxide linkages may be prepared by the oxidation of corresponding compounds containing —S-linkages. For example, the oxidation may conveniently be carried out by means of reaction with a peroxyacid, e.g. 3-chloroperbenzoic acid, preferably in an inert solvent, e.g. dichloromethane, preferably at or near room temperature, or alternatively by means of potassium hydrogen peroxomonosulphate in a medium such as aqueous methanol, buffered to acid pH5, at temperatures between about 0° C. and room temperature. This latter method is preferred for compounds containing an acid-liable group.

As another example of the interconversion process, compounds of formula (Ic), wherein T¹, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —N(R¹⁰)—SO₂—R¹⁵ or —N(R¹⁰)—SO₂—L⁴—R¹⁶ group (in which R¹⁰, R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined), may be prepared from the corresponding compounds of of formula (Ic) wherein T¹, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —NH₂ group by treatment with the appropriately substituted acid chloride Cl—SO₂—R¹⁵ or Cl—SO₂—L⁴—R¹⁶ (in which R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined), in the presence of a suitable base, such as triethylamine, in an inert solvent, such as tetrahydrofuran, and at a temperature at about room temperature.

As another example of the interconversion process, compounds of formula (I) containing sulphone linkages may be prepared by the oxidation of corresponding compounds containing —S— or sulphoxide linkages. For example, compounds of formula (Ib) wherein R¹⁸ is —SO₂Me may conveniently be prepared by means of reaction of compounds of formula (Ib) where R¹⁸ is —SMe with a peroxyacid, e.g. 3-chloroperbenzoic acid, preferably in an inert solvent, such as dichloromethane, at a temperature from about 0° C. to about room temperature.

As another example of the interconversion process, compounds of formula (Ib), wherein R⁴ and R⁵ are as hereinbefore defined and R¹⁸ a is —NY⁴Y⁵ group (in which Y⁴ is hydrogen and Y⁵ is as hereinbefore defined), may be prepared by reaction of compounds of formula (Ib), where R¹⁸ is a —SO₂Me group, with an appropriately substituted amine of formula Y⁵NH₂ (in which Y⁵ is as hereinbefore defined). The reaction may conveniently be carried out in an inert solvent such as dimethylformamide at a temperature up to about 100° C. When Y⁵ is hydrogen the reaction may be conveniently carried out in a sealed vessel. When Y⁵ is aryl, for example phenyl, the reaction may be conveniently carried out with the lithio-anion of the amine.

As another example of the interconversion process, compounds of formula (Ib), wherein R⁴ and R⁵ are as hereinbefore defined and R¹⁸ is a —OR¹⁷ group (in which R¹⁷ is as hereinbefore defined), may be prepared by reaction of compounds of formula (Ib), where R¹⁸ is a —SO₂Me group, with an appropriately substituted alcohol of formula R¹⁷OH (in which R¹⁷ is as hereinbefore defined). The reaction may conveniently be carried out in the presence of an alkali metal hydride, such as sodium hydride, in a mixture of inert solvents, for example tetrahydrofuran and dimethylformamide, and at a temperature at about room temperature.

It will be appreciated that compounds of the present invention may contain asymmetric centres. These asymmetric centres may independently be in either the R or S configuration. It will be apparent to those skilled in the art that certain compounds of the invention may also exhibit geometrical isomerism. It is to be understood that the present invention includes individual geometrical isomers and stereoisomers and mixtures thereof, including racemic mixtures, of compounds of formula (I) hereinabove. Such isomers can be separated from their mixtures, by the application or adaptation of known methods, for example chromatographic techniques and recrystallization techniques, or they are separately prepared from the appropriate isomers of their intermediates. Additionally, in situations where tautomers of the compounds of formula (I) are possible, the present invention is intended to include all tautomeric forms of the compounds.

According to a further feature of the invention, acid addition salts of the compounds of this invention may be prepared by reaction of the free base with the appropriate acid, by the application or adaptation of known methods. For example, the acid addition salts of compounds of this invention may be prepared either by dissolving the free base in water or an aqueous alcohol solution or other suitable solvents containing the appropriate acid and isolating the salt by evaporating the solution, or by reacting the free base and an acid in an organic solvent, such as tetrahydrofuran, in which case the salt separates directly or can be obtained by concentration of the solution.

Compounds of this invention can be regenerated from their acid addition salts by the application or adaptation of known methods. For example, parent compounds of the invention can be regenerated from their acid addition salts by treatment with an alkali, e.g. aqueous sodium bicarbonate solution or aqueous ammonia solution.

According to a further feature of the invention, base addition salts of the compounds of this invention may be prepared by reaction of the free acid with the appropriate base, by the application or adaptation of known methods. For example, the base addition salts of the compounds of this invention may be prepared either by dissolving the free acid in water or aqueous alcohol solution or other suitable solvents containing the appropriate base and isolating the salt by evaporating the solution, or by reacting the free acid and base in an organic solvent, in which case the salt separates directly or can be obtained by concentration of the solution.

Compounds of this invention can be regenerated from their base addition salts by the application or adaptation of known methods. For example, parent compounds of the invention can be regenerated from their base addition salts by treatment with an acid, e.g. hydrochloric acid.

Compounds of the present invention may be conveniently prepared, or formed during the process of the invention, as solvates (e.g. hydrates). Hydrates of compounds of the present invention may be conveniently prepared by recrystallization from water.

The starting materials and intermediates may be prepared by the application or adaptation of known methods, for example methods as described in the Reference Examples or their obvious chemical equivalents.

Intermediates of formula (II), wherein R¹ and R² are as hereinbefore defined, R¹⁹ is a 2-trimethylsilanyl-ethoxymethyl group and R²⁰ is —CH(OMe)₂, may be prepared by reaction of compounds of formula (II), wherein R¹ and R² are as hereinbefore defined, R¹⁹ is a 2-trimethylsilanyl-ethoxymethyl group and R²⁰ is —CHO, with trimethylorthoformate in the presence of an acid catalyst, such as 4-toluene sulphonic acid, in methanol at reflux temperature.

Intermediates of formula (II), wherein R¹ and R² are as hereinbefore defined, R¹⁹ is a 2-trimethylsilanyl-ethoxymethyl group and R²⁰ is —CHO, may be prepared by reaction of compounds of formula (1):

wherein R¹ and R² are as hereinbefore defined, R¹⁹ is a 2-trimethylsilanyl-ethoxymethyl group, with an alkyllithium, such as butyllithium or lithium diisopropylamide, in an inert solvent, such as tetrahydrofuran, at a temperature at about −78° C., followed by reaction with N-formylmorpholine.

Intermediates of formula (II), wherein R¹ and R² are as hereinbefore defined, R¹⁹ is hydrogen and R²⁰ is —CH(OMe)₂, may be prepared by reaction of compounds of formula (2):

wherein R¹ and R² are as hereinbefore defined, with glyoxal 1,1-dimethylacetal and ammonium acetate. The reaction may conveniently be carried out in a mixture of inert solvents, such as tert-butylmethyl ether and methanol, and at a temperature at about room temperature.

Intermediates of formula (II), wherein R¹, R² are as hereinbefore defined, R¹⁹ represents a —L¹—R⁷ or —L²—R⁸ group (in which R⁷, L¹ and L² is as hereinbefore defined and R⁸ is aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocycloalkyl) and R²⁰ is —CHO, may be similarly prepared by reaction of compounds of formula (1), wherein R¹, R² and R¹⁹ are as defined immediately above, with butyl lithium followed by reaction with N-formylmorpholine.

Intermediate 1,3-propanediols of formula (III), wherein R⁴ is an azidomethyl group, R⁵ is a methyl group, R⁶ is hydrogenated and m is 1, and where both R⁴ and R⁵ are attached in the 2-position, may be prepared by reaction of 5-azidomethyl-2,5-dimethyl-1,3-dioxane (prepared according to the procedure in J. Org. Chem., 1992, 57, page 6080) with a mineral acid, for example hydrochloric acid, in an aqueous organic solvent mixture such as tetrahydrofuran an water, at reflux temperature.

Intermediate 1,3-propanediols of formula (III), wherein R⁴ is an —NHC (═O)CF₃ group, R⁵ is a methyl group, R⁶ is hydrogen and m is 1, and where both R⁴ and R⁵ are attached in the 2-position, may be prepared by reaction of 2-amino-2-methyl-1,3-propanediol with trifluoroacetic acid in the presence of a base, such as potassium carbonate, in an inert solvent, such as dimethylformamide, and at a temperature at about room temperature.

Intermediate 1,3-propandiols of formula (III), wherein R⁴ is a —C(═O)—NY⁴Y⁵ group (in which Y⁴ and Y⁵ are as hereinbefore defined), R⁵ is a methyl group, R⁶ is hydrogen and m is 1, and where both R⁴ and R⁵ are attached in the 2-position, may be prepared by reaction of 2-carboxy-2-methyl-1,3-propanediol with an amine of formula HNY⁴Y⁵, wherein Y⁴ and Y⁵ are as hereinbefore defined. The coupling may conveniently be carried out with a carbodiimide, such as dicyclohexylcarbodiimide, in the presence of 1-hydroxybenzotriazole and diisopropylethylamine, in an inert solvent, such as acetonitrile, and at a temperature from room temperature to about 55° C. Other standard peptide coupling procedures may be employed for the reaction, such as those described hereinbefore.

Resins of formula Resin C in which R³, R⁵, R⁶ and m are as hereinbefore defined, and R⁴ contains a —C(═O)—NY⁴Y⁵ group may be prepared from the corresponding Resin C, in which R³, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —C(═O)—OR²¹ group (in which R²¹ is alkyl, aryl or aralkyl), by: (i) treatment with an alkali metal hydroxide, such as sodium hydroxide, in a mixture of water and a water miscible inert organic solvent, such as tetrahydrofuran, and at a temperature from about room temperature to about 70° C.; (ii) treatment of the resulting resin in which R⁴ contains a —C(═O)—OH group with oxalyl chloride solution in an inert solvent, such as dichloromethane, at a temperature at room temperature; (iii) treatment of the resulting resin in which R⁴ contains a —C(═O)—Cl group with an amine of formula HNY⁴Y⁵ in an inert solvent, such as dichloromethane, at a temperature at about room temperature.

Resins of formula Resin C in which R³, R⁵, R⁶ and m are as hereinbefore defined, and R⁴ contains a —N(R¹⁰)—C(═O)—R¹⁵ or —N(R¹⁰)—C(═O)—L⁴—R¹⁶ group (in which R¹⁰, R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined), may be prepared from the corresponding Resin C, in which R³, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —NH₂ group by treatment with the appropriately substituted acid chloride Cl—C(═O)—R¹⁵ or Cl—C(═O)—L⁴R¹⁶ (in which R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined), in the presence of triethylamine, in an inert solvent, such as tetrahydrofuran, and at a temperature at about room temperature.

Resins of formula Resin C in which R³, R⁵,R⁶ and m are as hereinbefore defined, and R⁴ contains a —N(R¹⁰)—SO₂—R¹⁵ or —N(R¹⁰)—SO₂—L⁴—R¹⁶ group (in which R¹⁰, R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined), may be prepared from the corresponding Resin C, in which R³, R⁵, R⁶ and m are as hereinbefore defined and R⁴ contains a —NH₂ group by treatment with the appropriately substituted acid chloride Cl—SO₂—R¹⁵ or Cl—SO₂—L⁴—R¹⁶ (in which R¹⁵, R¹⁶ and L⁴ are as hereinbefore defined), in the presence of triethylamine, in an inert solvent, such as tetrahydrofuran, and at a temperature at about room temperature.

Compound of formula (1), wherein R¹ and R² are as hereinbefore defined, R¹⁹ is a 2-trimethylsilanyl-ethoxymethyl group, may be prepared by reaction of compounds of formula (1), wherein R¹ and R² are as hereinbefore defined, R¹⁹ is a hydrogen atom, with 2-(trimethylsilyl)ethoxymethyl chloride in the presence of sodium hydride, in an inert solvent such as dimethylformamide, and at a temperature at about room temperature.

Compounds of formula (1) wherein R¹ and R² are as hereinbefore defined, R¹⁹ represents a group —L¹—R⁷ (where L¹ and R⁷ are as hereinbefore defined) or —L²—R⁸ (where L²is as hereinbefore defined and R⁸ is aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocycloalkyl) may be similarly prepared by reaction of compounds of formula (1), wherein R¹ and R² are as hereinbefore defined, R¹⁹ is a hydrogen atom, with an alkyl halide of formula (V) or (VI) respectively, in the presence of sodium hydride.

Compounds of formula (1), wherein R¹ and R² are as hereinbefore defined, R¹⁹ is a hydrogen atom, may be prepared by the application or adaptation of known literature methods, for example Boehm et. al., J. Med. Chem., 1996, 39, page 3829.

Intermediates of formulae (II), (III), (IV), Resin C and Resin D are novel compounds and, as such, they and their processes described herein for their preparation constitute further features of the present invention.

The present invention is further Exemplified but not limited by the following illustrative Examples and Reference Examples.

EXAMPLE 1

Compounds A, B and C

A solution of 4-[5-(4)-(4-fluoro-phenyl)-2-formyl-1-[(2-trimethylsilyl)ethoxy)methyl]-1H-imidazol-4(5)-yl]-pyridine (1:1 g, Reference Example 1), 1,1,1-tris(hydroxymethyl)-ethane (1.66 g) and pyridinium-4-toluenesulphonate (0.13 g) in dry toluene (20 ml) was gently refluxed for 20 hours with azetropic removal of water. After cooling to room temperature the reaction mixture was treated with ethyl acetate (100 ml), then washed three times with water (20 ml), then dried over magnesium sulphate and then evaporated. The residual oil was subjected to flash chromatography, on silica, eluting with a mixture of dichloromethane and methanol (24:1, v/v) to give {2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]-dioxan-5-yl}-methanol, cis-isomer, (Compound A) as a white solid, m.p. 270°-272°C. [Elemental analysis: C,64.22H,5.71; N10.81; F,4.91%. Calculated for C₂₀H₂₀FN₃.H₂O:—C,64.67; H,5.97; N,11.31; F,5.11%]; and {2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol, trans-isomer, (Compound B) as a buff-coloured solid, m.p. 250-250° C. [Elemental analysis: C,64.22; H,5.71; N,10.81; F,4.91%. Calculated: C,65.03; H,5.46; N,11.38; F,5.14%].

By proceeding in a similar manner but using 2,2-dimethyl-1,3-propanediol there was prepared 4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-1H-imidazol-4-yl]-pyridine. (Compound C) as a cream solid, m.p. 248-249° C. (with decomposition). [Elemental analysis: C,66.75; H,5.74; N,11.42%. Calculated for C₂₀H₂₀FN₃O₂.0.5H₂O: C,66.28; H,5.84; N,11.59%].

EXAMPLE 2

Compound D

A solution of 4-[2-(5-azidomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-1H-imdiazol-4-yl]pyridine, cis- and trans-isomers [1.56 g, Compound H] in methanol (100 ml) was treated with ammonium formate (1 g), then with 10% palladium on activated carbon (0.15 g). After stirring for 3.5 hours the reaction mixture was filtered through diatomaceous earth then evaporated. The residual orange solid was subjected to flash chromatography on silica eluting with a mixture of dichloromethane, pentane, methanol and concentrated ammonia (55:25:18:2 v/v/v/v) to give C-[5- methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-methylamine, cis- and trans-isomers, Compound D, (0.68 g) as a yellow solid.

EXAMPLE 3

Compounds E to Z

A stirred solution of 4-[2-dimethoxymethyl-5-(4)-(4-fluoro-phenyl)-1H-imidazol-4(5)-yl]-pyridine (5.75 g, Reference Example 3), and 2-methyl-2-trifluoroacetamide-1,3-propanediol (7.38 g, Reference Example 4) and 4-toluenesulphonic acid (8.03 g) in dry tetrahydrofuran (200 ml) was heated at reflux for 6 hours. After cooling the mixture was stood at room temperature for 4 days then partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic phase was washed twice with water (100 ml), then with brine (100 ml), then dried over magnesium sulphate and then evaporated to give 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-acetamide, cis- and trans-isomers (Compound E). The residue was subjected to flash chromatography on silica eluting with a mixture of dichloromethane and methanol (95:5, v/v) to give: 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-acetamide, cis-isomer (Compound F); MH⁺ 451; and 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluorophenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-acetamide, trans-isomer (Compound G). MH⁺ 451.

By proceeding in a similar manner but using 2-azidomethyl-2-methyl-1,3-propanediol (Reference Example 5) there was prepared 4-[2-(5-azidomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-1H-imidazol-4-yl]pyridine, cis- and trans-isomers (Compound H) as a white solid.

By proceeding in a similar manner but using 2-benzyl-1,3-propanediol and subjecting the crude product to preparative thick layer chromatography on silica eluting with a mixture of dichloromethane and methanol (9:1, v/v) there was prepared 4-[2-(5-benzyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-1H-imidazol-4-yl]-pyridine, cis- and trans-isomers (Compound I). R_(F) 0.46 using a mixture of dichloromethane and methanol (9:1 v/v). MH⁺ 416.

By proceeding in a similar manner but using methyl 2,2-bis(hydroxymethyl)propionate and subjecting the crude product to preparative thick layer chromatography on silica eluting with a mixture of dichloromethane and methanol (9:1, v/v) there was prepared 2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid methyl ester, cis- and trans-isomers (Compound J). R_(F) 0.71 using a mixture of dichloromethane and methanol (9:1 v/v). MH⁺ 398.

By proceeding in a similar manner but using 2,2-bis(hydroxymethyl)-tetrahydropyran, carrying out the reaction in dimethylformamide at 50° C. and subjecting the crude product to preparative thick layer chromatography on silica eluting twice with a mixture of dichloromethane and methanol (19:1, v/v) there was prepared 4-[5-(4-fluoro-phenyl)-2-(1,8,10-trioxa-spiro[5,5]undec-9-yl)-1H-imidazol-4-yl]-pyridine, (Compound K), as a mixture of isomers. R_(F) 0.45 and 0.48 using a mixture of dichloromethane and methanol (19:1, v/v) as eluent. MH⁺ 396.

By proceeding in a similar manner but using 2,2-bis(hydroxymethyl)-tetrahydrofuran, carrying out the reaction in dimethylformamide at 50° C. and subjecting the crude preparative thick layer chromatography on silica eluting twice with a mixture of dichloromethane and methanol (19:1, v/v) there was prepared 4-[5-(4-fluoro-phenyl)-2-(1,7,9-trioxa-spiro[4.5]dec-8-yl)-1H-imidazol-4-yl]-pyridine, (Compound L), as a mixture of isomers. R_(F) 0.39 and 0.45 using a mixture of dichloromethane and methanol (19:1, v/v) as eluent. MH⁺ 382.

By proceeding in a similar manner but using the appropriately substituted 1,3-propanediols, carrying out the reaction in dichloromethane at room temperature over 3 days, and subjecting the crude product to preparative thick layer chromatography on silica, there were prepared the Compounds M to Z depicted in Table 1. For Compounds M to V and Compound Z the eluent used was a mixture of dichloromethane and methanol (9:1, v/v); for Compound W the eluent used was ethyl acetate then a mixture of dichloromethane and methanol (14:1, v/v); and for Compounds X and Y the eluent used as a mixture of dichloromethane and methanol (14:1 v/v).

TABLE 1 MH⁺ STRUCTURE and substituted 1,3-propanediol MOLECULAR (intensity) Compound number used in the reaction R_(F) FORMULA (MS-ESI)

0.41 C19H18FN3O2 340 (100%)

0.40 C19H16FN3O2 338 (100%)

0.37 C18H16FN3O2 326 (100%)

0.40 C19H18FN3O2 340 (100%)

0.44 C20H20FN3O2 354  (50%) 169 (100%)

0.47 & 0.31 C25H22FN3O3 432 (100%)

0.20 & 0.18 C24H20FN3O2 402 (100%)

0.43 C23H26FN3O2 396 (100%)

0.30 C22H24FN3O2 382 (100%)

0.30 C23H22FN3O2 392 (100%)

0.14 C26H23FN4O3 459 (100%)

0.20 C26H23F2N5O2S 508 (100%)

0.25 & 0.18 C28H28FN5O2S 518 (100%)

0.31 C23H21FN4O2 405 (100%)

EXAMPLE 4

Compounds AA and AB

A solution of 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylmethyl]-acetamide, trans-isomer [1.04 g, Compound AC] and potassium carbonate (1.55 g) in methanol (150 ml) was heated at reflux for 24 hours. After cooling to room temperature the mixture was partitioned between ethyl acetate and water. The aqueous layer was treated with sodium chloride then extracted three times with ethyl acetate (50 ml). The compound organic phases were evaporated. The residual oil was subjected to flash chromatography on silica eluting with a mixture of dichloromethane, pentane, methanol and concentrated ammonia (55:25:18:2, v/v/v/v) to give C-[5-methyl-2-(5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl)-[1,3]dioxan-5-yl]-methylamine, trans-isomer (0.51 g, Compound AA). MH⁺ 369.

By proceeding in a similar manner but using 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylmethyl]-acetamide, trans-isomer, [Compound AB] there was prepared C-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-methylamine, cis-isomer (Compound AB). MH⁺ 369.

EXAMPLE 5

Compounds AC and AD

A suspension of C-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-methylamine (0.68 g, cis- and trans-isomers, Compound D) in dichloromethane (35 ml) was treated with triethylamine (0.72 ml) then with trfluoroacetic anhydride (0.72 ml). After stirring at room temperature for 4.5 hours the reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water, then with brine, then dried over magnesium sulphate and then evaporated. The residue was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and methanol (9:1, v/v) to give 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylmethyl]-acetamide, cis- and trans-isomers. The mixture was subjected to preparative HPLC, using methanol and water 40/60 to 5/95 v/v over 20 minutes to give 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylmethyl]-acetamide, trans-isomer (0.75 g, Compound AC, R_(T)=11.99,) and 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylmethyl]-acetamide, cis-isomer (0.3 g, Compound AD, R_(T)=10.8).

EXAMPLE 6

Compounds AE, AF and AG

A stirred solution of 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-acetamide, cis-isomer (1.75 g, Compound F) and potassium carbonate (1.07 g) in a mixture of methanol (200 ml) and water (5 ml) was heated at reflux for 8 hours. After coding to room temperature the mixture evaporated and then azeotroped with toluene. The residue was treating with silica and filtered through a pad of silica washing with a mixture of dichloromethane and methanol (4:1, v/v) to give 5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine, cis-isomer (1.3 g, Compound AE) as a yellow solid.

By proceeding in a similar manner but using Compound G there was prepared 5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine, trans-isomer (Compound AF).

By proceeding in a similar manner but using Compound E there was prepared 5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine, cis- and trans-isomers (Compound AG).

EXAMPLE 7

Compounds AH and AI

A solution of 2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid methyl ester, cis- and trans-isomers (0.34 g, Compound J) in methanol (15 ml) was treated with aqueous sodium hydroxide solution (1.71 ml, 1N) then heated at reflux for 7 hours. After cooling to room temperature the reaction mixture was evaporated. The residual cream powder was dissolved in methanol (10 ml) and the solution acidified to pH 5-6 by addition of glacial acetic acid. The resulting white precipitate was filtered and washed with pentane to give 2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid, trans-isomer (0.11 g, Compound AH). R_(F) 0.15 (CH₂Cl₂/CH₃OH, 9:1 developed five times), MH⁺ 384. The filtrate plus washings were absorbed onto silica and subjected to flash chromatography on silica eluting with a mixture of dichloromethane and methanol (9:1, v/v) to give 2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid, cis-isomer (0.14 g, Compound AI,) as a white solid. R_(F) 0.25 (CH₂Cl₂/CH₃OH, 9:1, developed five times), MH⁺ 384.

EXAMPLE 8

Compounds AJ to CO and FS to GD

A solution of 2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid, or trans-isomer (1 equivalent, Compound AH or AI) an appropriately substituted amine of formula HNY⁴Y⁵ [1.1 equivalents, see table 2], 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide [1.1 equivalents], 1-hydroxybenzotriazol hydrate [1.1 equivalents] and N,N-diisopropylethylamine [3 equivalents] in dry dimethylformamide was stirred at room temperature for 18 hours. The reaction mixture was evaporated and the residue was partitioned between ethyl acetate and water. The organic phase was washed with brine then evaporated to give Compounds AJ to GD and FS to GD depicted in Table 2 (Compound FV was obtained following alkaline hydrolysis of the intermediate ester). The R_(F) values indicated were determined using a mixture of dichloromethane and methanol (9:1, v/v) as eluent [* in one case a mixture of ethyl acetate and methanol (9:1, v/v) was used].

TABLE 2 MH⁺ STRUCTURE and MOLECULAR (In- Compound number HNY⁴Y⁵ R_(F) FORMULA tensity)

0.33 C27H25FN4O3 473  (70%) 418 (100%)

0.35 C27H25FN4O3 473  (20%) 418 (100%)

0.13 C22H23FN4O4 427 (100%)

0.28 C23H25FN4O4 441  (20%) 384 (100%)

NH₃ 0.14 C20H19FN4O3 383 (100%)

0.29 C26H24FN5O3 474 (100%)

0.18 C26H24FN5O3 474 (100%)

0.16 C26H24FN5O3 474 (100%)

0.09 C25H28FN5O3 466 (100%)

0.14 C25H30FN5O3 468 (100%)

0.25 C30H28FN5O3 526 (100%)

0.09 C23H25FN4O4 441 (100%)

0.32 C25H27FN4O4 467 (100%)

0.32 C24H25FN4O4 453 (100%)

0.39 C24H25FN4O3 437  (50%) 384 (100%)

0.33 C24H27FN4O3 439 (100%)

0.41 C26H31FN4O3 467 (100%)

0.29 C24H27FN4O4 455  (40%) 384 (100%)

0.33 C28H27FN4O3 487 (100%)

0.24 C27H26FN5O3 488 (100%)

0.32 C25H23FN4O4 463 (100%)

0.36 C25H27FN4O3 451  (30%) 384 (100%)

0.28 C22H23FN4O3 411  (11%) 384 (100%)

0.29 C23H25FN4O3 425  (70%) 384 (100%)

0.22 C23H23FN4O3 423  (25%) 384 (100%)

0.32 C25H27FN4O3 451 (100%)

0.36 C26H29FN4O3 465 (100%)

0.29 C23H25FN4O4 441 (100%)

0.18 C22H23FN4O4 427 (100%)

NH₃ 0.16 C20H19FN4O3 383 (100%)

0.25 C26H24FN5O3 474 (100%)

0.13 C26H24FN5O3 474 (100%)

0.10 C26H24FN5O3 474 (100%)

0.36 C24H25FN4O4 453 (100%)

0.08 C25H28FN5O3 466 (100%)

0.13 C25H30FN5O3 468 (100%)

0.28 C30H28FN5O3 526 (100%)

0.08 C23H25FN4O4 441 (100%)

0.37 C28H27FN4O3 487 (100%)

0.28 C24H27FN4O4 455 (100%)

0.25 C27H26FN5O3 488 (100%)

0.33 C25H23FN4O4 463 (100%)

0.34 C25H27FN4O4 467 (100%)

0.38 C24H25FN4O3 437  (10%) 384 (100%)

0.40 C25H27FN4O3 451  (60%) 384 (100%)

0.26 C23H25FN4O3 425  (40%) 384 (100%)

0.31 C24H27FN4O3 439 (100%)

0.24 C23H23FN4O3 423  (15%) 384 (100%)

0.32 C25H27FN4O3 451  (35%) 384 (100%)

0.32 C26H29FN4O3 465 (100%)

H₂N—CH₃.HCl 0.22 C21H21FN4O3 397  (50%) 384 (100%)

0.11 C24H28FN5O3 454 (100%)

0.33 C22H23FN4O3 411  (70%) 384 (100%)

0.40 C26H31FN4O3 467 (100%)

0.30 C22H23FN4O3 411  (60%) 384 (100%)

H₂N—CH₃.HCl 0.15 C21H21FN4O3 397  (45%) 384 (100%)

0.07 C24H28FN5O3 454  (40%) 418 (100%)

0.23 C22H23FN4O3 411  (34%) 384 (100%)

0.55 C27H29FN4O5 467 (100%)

0.71 C25H27FN4O4 509 (100%)

0.73 C28H31FN4O5 523 (100%)

0.29 C26H27FN4O5 495 (100%)

0.76 C24H25FN4O3S 469 (100%)

0.4 C24H25FN4O5S 501 (100%)

0.62 C26H29FN4O4 481 (100%)

0.59 C25H27FN4O4 467 (100%)

0.71 C26H29FN4O4 481 (100%)

0.53 C24H25FN4O4 453 (100%)

0.58* C26H29FN4O4 481 (100%)

0.72 C27H31FN4O4 495 (100%)

EXAMPLE 9

Compounds CP to DF

A solution of 5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine, cis- or trans-isomer (1 equivalent, Compound AE or AF), and an appropriately substituted isocyanate of formula O═C═N-R¹⁵ or O═C═N-L⁴-R¹⁶ [1 equivalent, see Table 3] in dry tetrahydrofuran was stirred at room temperature for 30 minutes. The reaction mixture was evaporated in vacuo to give Compounds CP to CZ depicted in Table 3. The R_(F) values indicated were determined using a mixture of dichloromethane and methanol (9:1, vv) as eluent.

By proceeding in a similar manner but using Compound AA or Compound AB, there were prepared Compounds DA to DF depicted in Table 3. The R_(F) values indicated were determined using a mixture of dichloromethane and methanol (9:1, v/v) as eluent.

TABLE 3 MH⁺ STRUCTURE and O═C═N—R¹⁵ or MOLECULAR (In- Compound number O═C═N—L⁴—R¹⁶ R_(F) FORMULA tensity)

0.46 C26H23FN5O3 474 (100%)

0.41 C22H24FN5O3 426 (100%)

0.41 C25H25FN6O4 493 (100%)

0.50 C27H26FN5O3 488  (70%) 423 (100%)

0.50 C26H26FN5O3S 508 (100%)

0.51 C28H26FN5O4 516 (100%)

0.40 C26H24FN5O3 474 (100%)

0.36 C27H24FN5O5 MH⁻ 516 (100%)

0.39 C27H26FN5O3 488 (100%)

0.24 C22H24FN5O3 426 (100%)

0.40 C26H26FN5O3S 508 (100%)

0.46 C28H28FN5O3 502 (100%)

0.39 C23H26FN5O3 440 (100%)

0.48 C27H26FN5O3 489 (100%)

0.42 C27H26FN5O3 488 (100%)

0.40 C28H28FN5O3 502 (100%)

0.23 C23H26FN5O3 440 (100%)

EXAMPLE 10

Compounds DG to DU

A solution of 5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine, cis- or trans-isomer (1 equivalent, Compound AE or AF), an appropriately substituted isothiocyanate of formula S═C═N-R¹⁵ or S═C═N-L⁴-R¹⁶ [1 equivalent, see Table 3] [1 equivalent] in dry tetrahydrofuran was heated to reflux for 18 hours. After cooling the reaction mixture was evaporated in vacuo and purified by preparative chromatography on silica gel, eluting with a mixture of dichloromethane and methanol (9:1 v/v) to give Compounds DG to DK depicted in Table 4. The R_(F) values indicated were determined using a mixture of dichloromethane and methanol (9:1, v/v) as eluent.

By proceeding in a similar manner but using Compound AA or Compound AB, there were prepared Compounds DL to DU depicted in Table 4. The R_(F) values indicated were determined using a mixture of dichloromethane and methanol (9:1, v/v) as eluent.

TABLE 4 MH⁺ STRUCTURE and S═C═N—R¹⁵ or MOLECULAR (In- Compound number S═C═N—L⁴—R¹⁶ R_(F) FORMULA tensity)

0.46 C26H31FN6O3S 527 (100%)

0.46 C25H24FN5O3S 494 (100%)

0.32 C25H23FN6O2S 491 (100%)

0.50 C28H26FN5O4S 548 (100%)

0.24 C27H24FN5O4S 534 (100%)

0.23 C26H25FN6O2S 505 (100%)

0.16 C27H33FN6O3S 541 (100%)

0.37 C26H26FN5O3S 508 (100%)

0.40 C29H28FN5O4S 562 (100%)

0.48 C29H28FN5O4S 562 (100%)

0.46 C26H26FN5O3S 508 (100%)

0.13 C28H26FN5O4S 548 (100%)

0.28 C26H25FN6O2S 505 (100%)

0.35 C27H33FN6O3S 541 (100%)

0.50 C28H26FN5O4S 548 (100%)

EXAMPLE 11

Compounds DV to EM

A stirred solution of 5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine, cis- or trans-isomer (1 equivalent, Compound AE or AF) and triethylamine [1 equivalent] in dry tetrahydrofuran was treated with an appropriately substituted acid chloride of formula Cl-C(═O)-R¹⁵ or Cl-C(═O)-L⁴-R¹⁶[1 equivalent, see Table 4]. After stirring at room temperature for 18 hours the reaction mixture was evaporated to give Compounds DV to ED depicted in Table 5. The R_(F) values indicated were determined using a mixture of dichloromethane and methanol (9:1, v/v) as eluent.

By proceeding in a similar manner using Compound AA or AA, there were prepared Compounds EF to EM depicted in Table 4. The R_(F) values indicated were determined using a mixture of dichloromethane and methanol (9:1, v/v) as eluent.

TABLE 5 MH⁺ STRUCTURE and Cl—C(═O)—R¹⁵ or MOLECULAR (In- Compound number Cl—C(═O)—L⁴—R¹⁶ R_(F) FORMULA tensity)

0.41 C21H21FN4O3 397 (100%)

0.42 C27H25FN4O3 473 (100%)

0.46 C26H29FN4O3 465 (100%)

0.58 C28H27FN4O4 MH⁻ 501 (100%)

0.52 C28H27FN4O4 503 (100%)

0.34 C21H21FN4O3 397 (100%)

0.49 C27H25FN4O3 473 (100%)

0.51 C26H29FN4O3 465 (100%)

0.52 C26H23FN4O3 459 (100%)

0.55 C29H29FN4O4 517 (100%)

0.33 C27H25FN4O3 473 (100%)

0.22 C22H23FN4O3 411 (100%)

0.30 C28H27FN4O3 486 (100%)

0.29 C27H31FN4O3 479 (100%)

0.18 C22H23FN4O3 411 (100%)

0.45 C28H27FN4O3 487 (100%)

0.45 C27H31FN4O3 479 (100%)

0.45 C27H25FN4O3 473 (100%)

EXAMPLE 12

Compounds EN to ER

A solution of 5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3-dioxan-5-ylamine, cis-isomer (1 equivalent, Compound AE), triethylamine (1.2 equivalents) and glutaric anhydride (1 equivalent) in dry tetrahydrofuran was heated to reflux for 8 hours. The reaction mixture was evaporated to give 4-{2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-butyric acid, cis-isomer (Compound EN). MH⁺469. R_(F) 0.12 {determined using a mixture of dichloromethane and methanol (9:1, v/v) as eluent}.

By proceeding in a similar manner but using Compound AB and glutaric anhydride, there was prepared 4-({2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-carbamoyl)-butyric acid, cis-isomer (Compound EO). MH⁺ 483. R_(F) 0.10 {determined using a mixture of dichloromethane, pentane, methanol and ammonia (55:25:18:2, v/v) as eluent}.

By proceeding in a similar manner but using Compound AE and succinic anhydride there was prepared 4-{2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-propionic acid, cis-isomer (Compound EP). MH⁺ 455. R_(F) 0.18 {determined using a mixture of dichloromethane and methanol (9:1, v/v) as eluent}.

By proceeding in a similar manner but using Compound AB and succinic anhydride there was prepared 4-({2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-carbamoyl)-propionic acid, cis-isomer (Compound EQ). MH⁺ 469. R_(F) 0.10 {determined using a mixture of dichloromethane, pentane, methanol and ammonia (55:25:18:2, v/v) as eluent}.

By proceeding in a similar manner but using Compound AA and succinic anhydride there was prepared 4-({5-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-carbamoyl)-propionic acid, trans-isomer (Compound ER). MH⁺ 469. R_(F) 0.11 {determined using a mixture of dichloromethane, pentane, methanol and ammonia (55:25:18:2, v/v) as eluent}.

EXAMPLE 13

Compounds ES to FB

A solution of 5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxane-5-ylamine, cis-isomer [1 -equivalent, Compound AE], and triethylamine [1 equivalent] in tetrahydrofuran was treated with methane sulphonyl chloride [1 equivalent]. After stirring at room temperature for 48 hours the reaction mixture was evaporated and the residue was subjected to preparative thick chromatography on silica, eluting with a mixture of dichloromethane and methanol (9:1, v/v), to give N-{2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanesulphonamide, cis-isomer (Compound ES). MH⁺ 433. R_(F) 0.42 {determined using a mixture of dichloromethane and methanol (9:1, v/v) as eluent}.

By proceeding in a similar manner but using Compound AA or Compound AB and an appropriately substituted sulphonyl chloride of formula Cl-SO₂-R¹⁵ or Cl-SO₂-L⁴-R¹⁵ there was prepared Compounds ET to FB depicted in Table 6. The R_(F) values indicated were determined using a mixture of dichloromethane and methanol (9:1, v/v) as eluent.

TABLE 6 STRUCTURE and Cl—SO₂—R¹⁵ or MOLECULAR MH⁺ EXAMPLE NUMBER Cl—SO₂—L⁴—R¹⁶ R_(F) FORMULA (Intensity)

0.21 C21H23FN4O4S 447 (100%)

0.28 C26H25FN4OS 509 (100%)

0.29 C27H27FN4O4S 523 (100%)

0.30 C24H23FN4O4S2 515 (100%)

0.30 C25H26FN5O5S 528 (100%)

0.32 C21H23FN4O4S 447 (100%)

0.53 C26H25FN4O4S 509 (100%)

0.50 C24H23FN4O4S2 515 (100%)

0.50 C25H26FN5O5S 528 (100%)

EXAMPLE 14

Compounds FC to FJ

A solution of ({2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-ethyl)-carbamic acid benzyl ester, trans-isomer (Compound FI) was treated with palladium, 5% activated on carbon and stirred at room temperature under a hydrogen atmosphere for 8 hours. The reaction mixture was filtered through a pad of diatomaceous earth and evaporated to dryness. The residue was subjected to preparative thick layer chromatography on silica, eluting with dichloromethane and methanol (7:3 v/v) to give 3-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-propionamide, trans-isomer (Compound FC). MH⁺ 426. R_(F) 0.04 determined using a mixture of dichloromethane and methanol (7:3, v/v) as eluent.

By proceeding in a similar manner but using Compound FJ there was prepared 3-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-propionamide, cis-isomer (Compound FD). MH⁺ 426. R_(F) 0.04 determined using a mixture of dichloromethane and methanol (7:3, v/v) as eluent.

By proceeding in a similar manner but using Compound FK there was prepared 4-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-butyramide, trans-isomer (Compound FE). MH⁺ 440. R_(F) 0.03 determined using a mixture of dichloromethane and methanol (7:3, v/v) as eluent.

By proceeding in a similar manner but using Compound FL there was prepared 4-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-butyramide, cis-isomer (Compound FF). MH⁺ 440. R_(F) 0.03 determined using a mixture of dichloromethane and methanol (7:3, v/v) as eluent.

By proceeding in a similar manner but using Compound FM there was prepared 2-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-4-yl}-acetamide, trans-isomer (Compound FG). MH³⁰ 412. R_(F) 0.01 determined using a mixture of dichloromethane and methanol (9:1, v/v) as eluent with two developments.

By proceeding in a similar manner but using Compound FN there was prepared 2-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide, cis-isomer (Compound FH). MH⁺ 412. R_(F) 0.03 determined using a mixture of dichloromethane and methanol (9:1, v/v) as eluent with two developments.

EXAMPLE 15

Compounds FI to FP

A solution of 5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine, cis- and trans-isomers [1 equivalent, Compound AG], N-benzyloxycarbonyl-β-alanine, [1 equivalent], 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride [1.1 equivalents], N,N-diisopropylethylamine [3 equivalents] and 1-hydroxybenzotriazole hydrate [1.1 equivalents] in dry dimethylformamide was heated at 90° C. for 2.5 hours. The reaction mixture was cooled to room temperature, then evaporated. The residue was partitioned between ethyl acetate (12 ml) and water (12 ml). The organic phase was separated and allowed to stand at room temperature. The solid which crystallised was filtered to give (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-ethyl)-carbamic acid benzyl ester, trans-isomer (Compound FI). The filtrate was subjected to preparative chromatography on silica, eluting with a mixture of dichloromethane and pentane (9:1, v/v) to give (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]-dioxan-5-ylcarbamoyl}-ethyl)-carbamic acid benzyl ester, cis-isomer (Compound FJ).

By proceeding in a similar manner but using N-benzyloxycarbonyl-4-aminobutyric acid there was prepared (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-propyl)-carbamic acid benzyl ester, trans-isomer. (Compound FK) and (3-{2-[4-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-propyl)-carbamic acid benzyl ester, cis-isomer (Compound FL).

By proceeding in a similar manner N-benzyloxycarbonylglycine there was prepared (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-methyl)-carbamic acid benzyl ester, trans-isomer (Compound FM) and (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-methyl)-carbamic acid benzyl ester, cis-isomer (Compound FN).

By proceeding in a similar manner but using 3-dimethylamino-propionic acid there was prepared 4-dimethylamino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-butyramide, cis- and trans-isomers Compound FO. MH⁺ 468. R_(F) 0.32 determined using a mixture of dichloromethane and methanol (7:3, v/v) as eluent.

EXAMPLE 16

Compound FP

A solution of {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, trans-isomer (7.43 g, Compound AW) in hot tetrahydrofuran (500 ml) was treated with a solution of methane sulphonic acid (1.578 g) in tetrahydrofuran. After standing at room temperature for 18 hours the reaction mixture was filtered and the solid recrystallised from acetonitrile with hot filtration through celite to give {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone methane sulphonic acid salt, trans-isomer (6.00 g, Compound FP) as a pale yellow crystalline solid, m.p. 242-246° C. (with decomposition). [Elemental analysis:- C,54.76; H, 5.25; N, 10.44; S, 5.89%. Calculated for C₂₄H₂₅FN₄O₄•CH₃SO₃H:- C,54.73; H,5.32; N,10.21; S,5.84%].

EXAMPLE 17

Compound FQ

A solution of N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-benzamide, trans-isomer (0.85 g, Compound FR) in tetrahydrofuran (100 ml) was treated with methane sulphonic acid (0.178 g). The reaction mixture was agitated for 5 minutes then evaporated to dryness and dried under high vacuum. The residual solid was recrystallised from ethyl acetate containing a minimum volume of acetonitrile to give N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-(1,3)dioxan-5-yl}-benzamide, methane sulphonic acid salt, trans-isomer (1.20 g, Compound FQ) as a yellow crystalline solid, m.p. 165-169° C. [Elemental analysis:- C,57.93; H,5.41; N,8.73%. Calculated for C₂₆H₂₃FN₄O₃•CH₃SO₃H•CH₃CO₂C₂H₅:- C,52.94; H,5.123; N,9.88%].

Compound FR

A stirred suspension of 5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine, trans isomer (1.76 g, Compound AF), benzoic acid (0.67 g) and diisopropylethylamine (1.39 ml) in dry dimethylformamide (50 ml) was treated with {0-(7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate} (1.88 g) under a nitrogen atmosphere. After stirring at room temperature for 2 hours the reaction mixture was evaporated to dryness. The residue was partitioned between ethyl acetate (70 ml) and saturated sodium bicarbonate (50 ml). The organic phase was washed twice with water (50 ml), then with brine (30 ml) and then evaporated. The residue was subjected to flash chromatography on silica eluting with ethyl acetate to give N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-benzamide, trans-isomer (0.85 g, Compound FR) as a cream coloured solid, m.p. 235-236° C. R_(F): 0.42 determined using a mixture of dichloromethane and methanol (9:1, v/v) as eluent. MH⁺ 459.

EXAMPLE 19

Compound AW

Method A: 2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid, trans-isomer (7.70 g, Compound AH) was added portionwise to stirred thionyl chloride. The reaction mixture was stirred at room temperature for 1.25 hours then evaporated. The residue was azeotroped with dry toluene to yield the crude acid chloride. This was treated with dry dichloromethane (150 ml) followed by morpholine (30 ml) under nitrogen. The mixture was stirred at room temperature for 2.5 hours then evaporated. The residue was partitioned between ethyl acetate (250 ml) and saturated sodium bicarbonate (200 ml). The insoluble product at the interface was filtered off and washed with methanol (10 ml), then with water (20 ml) and then with diethyl ether (20 ml) to give {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-yl}-morpholin-4-yl-methanone, trans-isomer (7.63 g, Compound AW), m.p. 288-291° C. MH⁺ 453.

Method B: 4-[2-(Dimethoxymethyl)-5-(4-fluorophenyl)-1H-4-imidazolyl]pyridine (62.7 g) and 3-hydroxy-2-(hydroxymethyl)-2-methyl-1-morpholino-1-propanone (44.8 g, Reference Example 6) were added to toluene (440 ml), under nitrogen. The mixture was stirred and heated to reflux under a Dean and Stark trap for 20 minutes. N,N-dimethylformamide (160 ml) and methanesulphonic acid (2 ml were added and the mixture heated to a gentle reflux over 4 hours, removing a total of 150 ml distillate at a fairly uniform rate. The reaction mixture was then evaporated in vacuo to remove as much toluene as possible. The resulting suspension was treated with triethylamine (8 ml) and then water (600 ml) was added dropwise over 1 hour. The mixture was filtered to give a damp, crude solid mixture of cis- and trans-isomers after washing with water and allowing the cake to suck on the filter for 1 hour. This material was stirred in methanol (350 ml), then the mixture was heated to reflux for 15 minutes and then cooled to 5° C. The solid was filtered and then washed with methanol to give {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, trans-isomer (46.4 g, Compound AW), m.p. 214° C. (with decomposition). ¹H NMR (δ, CDCl₃); 8.52 (d, 0.6H); 8.39 (d, 1.4H); 7.32-7.49 (m, 4H); 7.29 (t, 1.4H); 7.13 (t, 0.6H); 5.59 (s, 1H); 4.07 (s, 4H); 3.51 (bd, 8H); 1.56 (s, 3H).

EXAMPLE 20

Compound GE

A stirred suspension of {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-4-yl}-morpholin-4-yl-methanone, trans-isomer (4.52 g, Compound AW) in a mixture of ethanol and methanol (45 ml, 95:5, v/v) was treated with aqueous hydrobromic acid (1.2 ml, 48%). The mixture was heated to reflux, then water (15 ml) was added and then the mixture was heated again to reflux. The solution formed was allowed to cool to room temperature then filtered. The solid was washed three times with a mixture of ethanol and methanol (10 ml, 95:5, v/v) to give {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone monohydrobromide dihydrate, trans-isomer (4.5 g, Compound GE) as an off-white crystalline solid, m.p. 276-277° C. (with decomposition ). ¹H NMR (CD₃)₂SO: δ1.53 (s, 3H), 3.49 (bd, 8H), 4.08 (s, 4H), 5.64 (s, 1H), 7.36 (t, 2H), 7.53-7.58 (m, 2H), 7.84 (d, 2H), 8.63 (d, 2H).

EXAMPLE 21

Compound GF

{2-[4-(4-Fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, trans-isomer (25.2 g, Compound AW), stirred in isopropanol (300 ml), was treated with concentrated hydrochloric acid (5 ml) and water (440 ml) and the mixture was heated to reflux for 15 minutes. The mixture was cooled to room temperature and then filtered. The solid was washed with isopropanol to give {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone monohydrochloric dihydrate, trans-isomer (22.5 g, Compound GF) as an off-white solid, m.p. 245-248° C. (with decomposition). ¹H NMR (CD₃)₂SO; δ 1.58 (s, 3H), 3.55 (bd, 8H), 4.12 (s, 4H), 5.68 (s, 1H), 7.49 (t, 2H), 7.58-7.62 (m, 2H), 7.89 (d, 2H), 8.68 (d, 2H).

EXAMPLE 22

Compound GG

{2-[4-(4-Fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, trans-isomer (4.52 g, Compound AW), stirred in a mixture of ethanol and methanol (45 ml, 95:5, v/v), was treated with d-10-camphorsulphonic acid (2.55 g). The mixture was heated to reflux and the resulting solution allowed to cool to room-temperature. The resulting solid was collected by filtration and washed three times with a mixtures of ethanol and methanol (10 ml, 95:5, v/v) to give {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone d-10-camphorsulphonic acid salt, trans-isomer (6.0 g, Compound GG) as pale yellow crystals, m.p. 265-267° C. (with decomposition). ¹H NMR (CD₃)₂SO: δ 0.74 (s, 3H), 1.05 (s, 3H), 1.33-1.43 (m, 2H), 1.58 (s, 3H), 1.80 (d, 1H), 1.81-1.89 (m, 1H), 1.94 (t, 1H), 2.24 (dt, 1H), 2.49 (d, 1H), 2.64-2.72 (m, 1H), 2.89 (d, 1H), 33.53 (d, 8H), 4.12 (s, 4H), 5.69 (s, 1H), 7.40 (t, 2H), 7.57-7.63 (m, 2H), 7.90 (d, 2H), 8.68 (d, 2H).

EXAMPLE 23

Compounds GH to HK

-   (a) A solution of     {2-[4-(4-fluoro-phenyl)-5-(2-methanesulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans isomer (1 equivalent, Compound KH) and cyclopropylamine (5     equivalents) in dry dimethylformamide was heated at 100° C. for 16     hours. The solvent was evaporated and the residue subjected to high     pressure liquid chromatography on a C18 Dynamax 60 Å column using     gradient elution with a mixture of acetonitrile and water as the     mobile phase (0-2 minutes 20% acetonitrile; 3-16 minutes ramp up to     80% acetonitrile; 17 minutes to end of run 80% acetonitrile) and UV     detection at 238 nm to give     {2-[5-(2-cyclopropylaminopyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans isomer (Compound GH), HPLC retention time=8.0 minutes. MH⁺     509. -   (b) By proceeding in a similar manner to Example 23(a), but     replacing cyclopropylamine with an appropriately substituted amine     of formula HNY⁴Y⁵ [5 equivalents, see Table 7], there were prepared     Compounds GI to HK in Table 7. For Compound GI the reaction was     carried out in the absence of dimethylformamide in a sealed vessel.     For Compound GW the lithio-anion of the aniline (generated by     reaction of aniline with butyl lithium in tetrahydrofuran according     to standard reaction conditions) was used to replace the     cyclopropylamine. Compounds GI to GL were obtained as solids on     treating the crude reaction product with acetonitrile. The R_(T)     values indicated in Table 7 refer to high pressure liquid     chromatography retention times determined on a C18 Dynamax 60Å     column using gradient elution with a mixture of acetonitrile and     water as the mobile phase (0-12 minutes 5% acetonitrile ramp up to     80% acetonitrile; 12 minutes to end of run 80% acetonitrile). The     R_(F) values indicated in Table 7 were determined using a mixture of     ethyl acetate and methanol (19:1, v/v) [the eluant for Compounds HJ     and HK was a mixture of dichloromethane and methanol (9:1, v/v)].

TABLE 7 STRUCTURE and MOLECULAR MH⁺ Compound number HNY⁴Y⁵ R_(T) R_(F) FORMULA (Intensity)

NH₃ 9 C23H25FN6O4 469 (100%)

0.5 C25H29FN6O4 497 (100%)

0.07 C26H31FN6O5 527 (100%)

0.19 C26H31FN6O5 527 (100%)

H₂N— 9 C24H27FN6O4 483 (100%)

10 C31H38FN7O6 624 (100%)

11 C29H35FN6O4 551 (100%)

8 C25H29FN6O5 513 (100%)

6 C25H30FN7O4 512 (100%)

7 C29H33FN8O4 577 (100%)

7 C30H38FN7O5 596 (100%)

11 C30H31FN6O4 559 (100%)

11 C31H33FN6O4 573 (100%)

11 C31H33FN6O4 573 (100%)

11.5 C29H29FN6O4 545 (100%)

10 C28H33FN6O4 537 (100%)

7 C29H30FN7O4 560 (100%)

7 C29H30FN7O4 560 (100%)

7 C29H30FN7O4 560 (100%)

10.5 C28H29FN6O5 549 (100%)

13 C28H29FN6O4S 565 (100%)

9 C28H33FN6O5 553 (100%)

7 C28H34FN7O4 552 (100%)

9 C27H31FN6O5 539 (100%)

8 C27H33FN6O5 541 (100%)

7 C28H36FN7O4 554 (100%)

7 C27H34FN7O4 540 (100%)

0.22 C25H27FN6O6 527 (100%)

0.24 C26H29FN6O6 541 (100%)

-   -   (c) By proceeding in the same manner to Example 23 (b) and using         the appropriately substituted amine of formula HNY⁴Y⁵ there are         prepared Compounds A1 to A16.         {2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,         trans-isomer, (Compound A1);         {2-[5-(2-allylamino-pyrimidin-4-yl]4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,         trams-isomer, trams-isomer, (Compound A2);         {2-[5-(2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl)-5-methyl-[1,3]-dioxan-5-yl         )-morpholin-4-yl-methanone, trams-isomer, (Compound A3);         (4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(morpholine-4-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl)-pyrimidin-2-ylamino)-acetonitrile,         trams-isomer, (Compound A4);         3-(4-(5-(4-fluoro-phenyl)-2-[5-methyl-5-(morpholine-4-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionitrile,         trans-isomer, (Compound A5);         (2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxin-5-yl)-morpholin-4-yl-methanone,         trans-isomer, (Compound A6);         (2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxin-5-yl)-morpholin-4-yl-methanone,         trams-isomer, (Compound A7);         2-(4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-morpholine-4-carbonyl)-[1,3]dioxin-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetamide,         trams-isomer, (Compound A5);         3-(4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(morpholine-4-carbonyl)-[1,3)dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionamide,         trams-isomer, (Compound A9);         {2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl)-5-methyl-[1,3]dioxin-5-yl}-morpholin-4-yl-methanone,         trams-isomer, (Compound A10);         {2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,         trams-isomer, (Compound A11);         2-[5-(2-(4-fluorobenzyl)amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl)-5-methyl-[1,3]dioxin-5-yl}-morpholin-4-yl-methanone,         trans-isomer, (Compound A12);         2-[5-(2-(4-methoxybenzyl)amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxin-5-yl}-morpholin-4-yl-methanone,         trams-isomer, (Compound A13);         {2-[4-(4-fluoro-phenyl)-5-(2-(4-fluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxin-5-yl)-morpholin-4-yl-methanone,         trams-isomer, (Compound A14);         {2-[4-(4-fluoro-phenyl)-5-(2-(3,4-difluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,         trans-isomer, (Compound A15);         {2-[4-(4-fluoro-phenyl)-5-(2-(3-methoxyphenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxin-5-yl}-morpholin-4-yl-methanone,         trans-isomer, (Compound A16);     -   (d) By Proceeding in a similar manner to Example 23 (b) but         using         2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5,5-dimethyl-[1,3]dioxane         (Compound KI) then were prepared Compounds HL to IN in Table 7a.

TABLE 7a STRUCTURE and MOLECULAR MH⁺ COMPOUND NUMBER HNY⁴Y⁵ R_(T) FORMULA (Intensity)

NH₃ 10.31 C19H20FN5O2 370 (100%)

10.58 C20H22FN5O2 384 (100%)

10.88 C21H24FN5O2 398 (100%)

11.05 C22H24FN5O2 410 (100%)

12.7 C25H30FN5O2 452 (100%)

9.76 C21H24FN5O3 414 (100%)

8.85 C21H25FN6O2 413 (100%)

9.16 C25H25FN7O2 478 (100%)

9.15 C26H33FN6O3 497 (100%)

9.68 C22H26FN5O2 428 (100%)

12.4 C26H26FN5O2 446 (100%)

13.01 C27H28FN5O2 474 (100%)

13.01 C27H28FN5O2 474 (100%)

12.53 C25H24FN5O2 446 (100%)

12.23 C24H28FN5O2 438 (100%)

8.97 C25H25FN6O2 461 (100%)

8.87 C25H25FN6O2 461 (100%)

8.94 C25H25FN6O2 461 (100%)

11.99 C24H24FN5O3 450 (100%)

12.3 C24H24FN5O2S 466 (100%)

11.29 C24H28FN5O3 454 (100%)

9.43 C24H29FN6O2 453 (100%)

11.1 C23H26FN5O3 440 (100%)

11.1 C23H28FN5O3 442 (100%)

10.78 C22H26FN5O3 428 (100%)

9.07 C24H31FN6O2 455 (100%)

9.14 C23H29FN6O2 441 (100%)

-   -   (e) By proceeding in a similar manner to Example 23 (d) and         using the appropriately substituted amine of formula HNY⁴Y⁵         there are prepared Compounds A17 to A35.         {4-[2-(5,5-dimethyl-[1.3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl)-pyrimidin-2-ylamino}-acetic         acid, (Compound A17);         3-[4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-yl)-pyrimidin-2-ylamino)-propionic         acid, (Compound A18);         {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-piperidin-4-yl-amine,         (Compound A19);         {4-[2-(5,5-dimethyl-[1,3]dioxin-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-isopropyl-amine,         (Compound A20);         allyl-{4-(2-(5,5-dimethyl-[1,3]dioxin-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl-amine,         (Compound A21),;         cyclopropylmethyl-{4-[2-(5,5-dimethyl-[1,3]dioxin-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,         (Compound A22);         {4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino)-acetonitrile,         (Compound A23);         3-{4-[2-(5,5-dimethyl-[1,3]dioxin-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionitrile,         (Compound A24);         {4-[2-(5,5-dimethyl-[1,3]dioxin-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-3-yl-amine,         (Compound A25);         {4-[2-(5,5-dimethyl-[1,3]dioxin-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-4-yl-amine,         (Compound A26);         2-{4-[2-(5,5-dimethyl-[1,3]dioxin-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl)-pyrimidin-2-ylamino}-acetamide,         (Compound A27);         3-(4-(2-(5,5-dimethyl-[1,3]dioxin-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino)-propionamide,         (Compound A28);         {4-[2-(5,5-dimethyl-[1,3]dioxin-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-propylamine,         (Compound A29);         4-[2-(5,5-dimethyl-[1,3]-dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-pyrrolidin-1-yl-pyrimidine,         (Compound A30);         4-fluorobenzyl-{4-[2-(5,5-dimethyl-[1,3]dioxin-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,         (Compound A31);         4-methoxybenzyl-{4-(2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl)-pyrimidin-2-yl}-amine,         (Compound A32);         {4-[2-(5,5-dimethyl-[1,3]dioxin-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-4-fluorophenyl-amine,         (Compound A33);         {4-[2-(5,5-dimethyl-[1,3]dioxin-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl)-pyrimidin-2-yl)-3,4-difluorophenyl-amine,         (Compound A34);         {4-[2-(5,5-dimethyl-[1,3]dioxin-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl)-3-methoxyphenyl-amine,         (Compound A35);     -   (f) By proceeding in a similar manner to Example 23 (a), but         using         [2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl)-methanol,         trans isomer, (Compound KJ) and replacing cyclopropylamine with         liquid ammonia and carrying out the reaction under pressure for         2 days, there was prepared following preparative thin layer         chromatography on silica gel [eluting with a mixture of         dichloromethane, methanol and ammonia (90-10:2,         v/v/v)]{2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trans-isomer (Compound IO) as a white solid. MH⁺ 386, R_(F):         0.41 (solvent as described immediately above).     -   (g) By proceeding in a similar manner to Example 23 (b) but         using         {2-[4-[4-fluoro-phenyl)-5-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]-dioxan-5-yl}-methanol,         trans isomer, (Compound KJ) there are prepared Compounds A36 to         A79:-         {2-(4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl)-methanol,         trans-isomer, (Compound A36);         {2-(5(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A37);         {2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A38);         (2-(4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl)-methanol,         trans-isomer, (Compound A39);         {2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl         )-methanol, trans-isomer, (Compound A40);         2-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-5-methyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino)-ethanol,         trans-isomer, (Compound A41);         {2-[5-[2-(2-aminoethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl)-methanol,         trans-isomer, (Compound A42);         [2-(4-(4-fluoro-phenyl)-5-(2-(3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-methanol,         trans-isomer, (Compound A43);         (2-(4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl)-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl)-methanol,         trans-isomer, (Compound A44);         3-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-5-methyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino)-propan-1-d,         trans-isomer, (Compound A45);         {2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A46);         {2-[5(2-(4-fluorobenzyl)amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A47);         {2-{5(2-(4-methoxybenzyl)amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl)-methanol,         trans-isomer, (Compound A48);         (2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-methanol,         R isomer, trans-isomer, (Compound A49);         (2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-methanol,         S isomer, trans-isomer, (Compound A50);         {2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A51);         {2-[4-(4-fluoro-phenyl)-5-(2-(4-fluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A52);         {2-[4-(4-fluoro-phenyl)-5-(2-(3,4-difluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A53);         {2-[4-(4-fluoro-phenyl)-5-(2-(3-methoxyphenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A54);         {2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A55);         [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-methanol,         trans-isomer, (Compound A56);         [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino)-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-methanol,         trans-isomer, (Compound A57);         [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-methanol,         trans-isomer. (Compound A58);         [2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-methanol,         trans-isomer, (Compound A59);         [2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-methanol,         trans-isomer, (Compound A60);         [2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl)-methanol,         trans-isomer, (Compound A61);         (2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl)-methanol,         trans-isomer, (Compound A62);         {2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A63);         (2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-methanol,         trans-isomer, (Compound A64);         (2-{4(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazo[-2-yl}-5-methyl-[1.3]dioxan-5-yl)-methanol,         trans-isomer, (Compound A65);         {2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A66);         {2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A67);         {4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-5-methyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic         acid, trams-isomer, (Compound A68);         3-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-5-methyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic         acid, trams-isomer, (Compound A69);         {2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A70);         {2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A71);         {2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A72);         {4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-5-methyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl)-pyrimidin-2-ylamino}-acetonitrile,         trams-isomer, (Compound A73);         3-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-5-methyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino)-propionitrile,         trams-isomer, (Compound A74);         (2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-methanol,         trams-isomer, (Compound A75);         (2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl         }-5-methyl-[1,3]dioxan-5-yl)-methanol, trans-isomer, (Compound         A76);         2-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-5-methyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetamide,         trams-isomer, (Compound A77);         3-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-5-methyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionamide,         trams-isomer, (Compound A78);         {2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A79);     -   (h) By proceeding in a similar manner to Example 23 (g) but         using         {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl}-methanol,         cis-isomer, (Compound KK) there are prepared the corresponding         cis-isomers of Compounds A36 to A79.     -   (i) By proceeding in a similar manner to Example 23 (b) but         using         2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methylene-[1,3]dioxane         (Compound KL) there are prepared compounds A80 to A125:-         4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamine,         (Compound A80);         {4-(5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-methyl-amine,         (Compound A81);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-dimethyl-amine,         (Compound A82);         cyclopropyl-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,         (Compound A83);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-piperidin-4-yl-amine,         (Compound A84);         cyclohexyl-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,         (Compound A85);         2-{4-[-5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-ethanol,         (Compound A86);         N1-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-ethane-1,2-diamine,         (Compound A87);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-[3H-imidazol-4-yl)-pyrimidin-2-yl}-(3-(5H-imidazol-1-yl)-propyl]-amine,         (Compound A88);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(3-morpholin-4-yl-propyl)-amine,         (Compound A89);         3-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propan-1-ol,         (Compound A90);         benzyl-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,         (Compound A91);         4-fluorobenzyl-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine         , (Compound A92);         4-methoxybenzyl-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine         , (Compound A93);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(1-phenyl-ethyl)-amine,         R isomer, (Compound A94);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(1-phenyl-ethyl)-amine,         S isomer, (Compound A95);         {4-(5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-phenyl-amine,         (Compound A96);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-4-fluorophenyl-amine         , (Compound A97);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-3,4-difluorophenyl-amine,         (Compound A98);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-3-methoxyphenyl-amine,         (Compound A99);         4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-2-piperidin-1-yl-pyrimidine,         (Compound A100);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-4-ylmethyl-amine,         (Compound A101);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-3-ylmethyl-amine,         (Compound A102);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-2-ylmethyl-amine,         (Compound A103);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-indazol-4-yl]-pyrimidin-2-yl}-(furan-2-ylmethyl)-amine,         (Compound A104);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(thiophen-2-ylmethyl)-amine,         (Compound A105);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(tetrahydro-furan-2-ylmethyl)-amine,         (Compound A106);         4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-2-(4-methyl-piperazin-1-yl)-pyrimidine,         (Compound A107);         4-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl         }-morpholine, (Compound A108);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(3-methoxy-propyl)-amine,         (Compound A109);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(2-methoxy-ethyl)-amine,         (Compound A110);         N-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-N′,N′-dimethyl-propane-1,3-diamine,         (Compound A111);         N-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl)-N′,N′-dimethyl-ethane-1,2-diamine,         (Compound A112);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic         acid, (Compound A113);         3-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic         acid, (Compound A114);         {4-(5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-isopropyl-amine,         (Compound A115);         allyl-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,         (Compound A116);         cyclopropylmethyl-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl)-pyrimidin-2-yl}-amine,         (Compound A117);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino]-acetonitrile,         (Compound At 118);         3-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl)-pyrimidin-2-ylamino}-propionitrile,         (Compound A119);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4yl]-pyrimidin-2-yl}-pyridin-3-yl-amine,         (Compound A120);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-4-yl-amine,         (Compound A121);         2-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetamide,         (Compound A122);         3-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionamide,         (Compound A123);         {4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-propyl-amine,         (Compound A124);         4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxin-2-yl)-3H-imidazol-4-yl]-2-pyrrolidin-1-yl-pyrimidine,         (Compound A125);     -   (j) By proceeding in a similar manner to Example 23 (b) but         using 4-(2-[1,3]dioxan-2         yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-methylsulphonyl-pyrimidine         (Compound KM) there are prepared Compounds A126 to A170:-         4-[2-[1,3]dioxin-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamine,         (Compound A126);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-methyl-amine,         (Compound A127);         {4-[2-[1,3]dioxin-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-dimethyl-amine,         (Compound A128);         cyclopropyl-{4-[2-[1,3]dioxin-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-Pyrimidin-2-yl}-amine,         (Compound A129);         {4-[2-[1,3]dioxin-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl)-pyrimidin-2-yl}-piperidin-4-yl-amine,         (Compound A130);         cyclohexyl-{4-[2-[1,3]dioxin-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl}-pyrimidin-2-yl}-amine,         (Compound A131),         2-{4-[2-[1,3]dioxin-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-ethanol,         (Compound A132);         N1-{4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl)-pyrimidin-2-yl)-ethane-1,2-(amine,         (Compound A133);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl)-pyrimidin-2-yl}-[3-(5H-imidazol-1-yl)-propyl]-amine,         (Compound A134);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl)-pyrimidin-2-yl}[3-morpholin-4-yl-propyl)-amine,         (Compound A135);         3-{4-(2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propan-1-ol,         (Compound A136);         benzyl-{4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,         (Compound A137);         4-fluorobenzyl-(4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,         (Compound At 138);         4-methoxybenzyl-{4-[2-[1,3]]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,         (Compound A139);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(1-phenylethyl)-amine,         R isomer, (Compound A140);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(1-phenylethyl)-amine,         S isomer, (Compound A141);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4yl]-pyrimidin-2-yl}-phenyl-amine,         (Compound A142);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(4-fluorophenyl)-amine,         (Compound A143);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(3,4-difluorophenyl)-amine,         (Compound A144);         {4-[-2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(4-methoxyphenyl)-amine,         (Compound A145);         4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-piperidin-1-yl-pyrimidine,         (Compound A146);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-4-ylmethyl-amine,         (Compound A147);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl         -pyrimidin-2-yl}-pyridin-3-ylmethyl-amine, (Compound A148);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-2-ylmethyl-amine,         (Compound A149);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl-}-(furan-2-ylmethyl)-amine         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(thiophen-2-ylmethyl)-amine,         (Compound A150);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(tetrahydro-furan-2-ylmethyl)-amine,         (Compound A151);         4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-(4-methyl-piperazin-1-yl)-pyrimidine,         (Compound A152);         4-{4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-morpholine,         (Compound A153);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl-3H-imidazol-4-yl]-pyrimidin-2-yl}-(3-methoxy-propyl)-amine,         (Compound A154);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(2-methoxy-ethyl)-amine,         (Compound A155);         N-{4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-N′,N′-dimethyl-propane-1,3-diamine,         (Compound A156);         N-{4-[2-[1,3]dioxan-2-y-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-N′,N′-dimethyl-ethane-1,2-diamine,         (Compound A157);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic         acid, (Compound A158);         3-{4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic         acid, (Compound A159);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-isopropyl-amine,         (Compound A160);         allyl-{4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,         (Compound A161);         cyclopropylmethyl-{4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,         (Compound A162);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetonitrile,         (Compound A163);         3-{4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionitrile,         (Compound A164);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-3-yl-amine,         (Compound A165);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-4-yl-amine,         (Compound A166);         2-{4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetamide,         (Compound A167);         3-{4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionamide,         (Compound A168);         {4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-propyl-amine,         (Compound A169);         4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-pyrrolidin-1-yl-pyrimidine,         (Compound A170);     -   (k) By proceeding in a similar manner to Example 23 (b) but         using         {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trans-isomer; (Compound KN) there are prepared Compounds A171 to         A215:-         {2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A171);         {2-[4-(4-fluoro-phenyl)-5(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A172);         {2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methano),         trans-isomer, (Compound A173);         {2-[5-(2-cyclopropylamino-pyrimidin-4-yl)4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A174);         (2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl)-1H-imidazol-2-yl}-[1,3]dioxan-5-yl)-methanol,         trans-isomer, (Compound A175);         {2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A176);         2-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-[1,3)dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino)-ethanol,         trans-isomer, (Compound A177);         {2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-[-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A178);         [2-(4-(4-fluoro-phenyl)-5-[2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-[1,3]dioxan-5-yl]-methanol,         trans-isomer, (Compound A179);         (2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-methanol,         trans-isomer, (Compound A180);         3-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino)-propan-1-ol,         trans-isomer, (Compound A181);         {2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trans-isomer, (Compound A182);         {2-[5-(2-(4-fluorobenzyl)amino-pyrimidin-4yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A183);         {2-[5-(2-(4-methoxybenzyl)amino-pyrimidin-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A184);         (2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylaminopyrimidin-4-yl]-1H-imidazol-2-yl}-[1,3]dioxan-5-yl)-methanol,         R isomer, trams-isomer, (Compound A185);         (2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-y}-[1,3]dioxan-5-yl)-methanol,         S isomer, trams-isomer, (Compound A186);         {2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3)dioxan-5-yl}-methanol,         trams-isomer, (Compound A187);         {2-[4-(4-fluoro-phenyl)-5-(2-(4-fluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A188);         {2-[4-(4-fluoro-phenyl)-5-(2-(3,4-difluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A189);         {2-[4-(4-fluoro-phenyl)-5-(2-(4-methoxyphenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A190);         {2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A191);         [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-[1,3]dioxan-5-yl]-methanol,         trams-isomer, (Compound A192);         [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-[1,3]dioxan-5-yl]-methanol,         trams-isomer, (Compound A193);         [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-[1,3]dioxan-5-yl]-methanol,         trams-isomer, (Compound A194);         [2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-[1,3]dioxan-5-yl]-methanol,         trams-isomer, (Compound A195);         [2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-[1,3]dioxan-5-yl]-methanol,         trams-isomer, (Compound A196);         [2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-[1,3]dioxan-5-yl]-methanol,         trams-isomer, (Compound A197);         (2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl)-1H-imidazol-2-yl}-[1,3]dioxan-5-yl)-methanol,         trams-isomer, (Compound A198);         {2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A199);         (2-[4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-[1,3]dioxan-5-yl)-methanol,         trans-isomer, (Compound A200);         (2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl)-1H-imidazol-2-yl}-[1,3]dioxan-5-yl)-methanol,         trams-isomer, (Compound A201);         {2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl-methanol,         trans-isomer, (Compound A202);         {2-[5-[2-(3-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl-methanol,         trans-isomer, (Compound A203);         {4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetetic         acid, trans-isomer, (Compound A204);         3-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic         acid, trans-isomer, (Compound A205);         (2-{4-(4-fluoro-phenyl)-5-(2-isopropylalimino-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A206);         {2-[5-(2-allylamino-pyrimidin-4yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A207);         {2-[5-[2-(isopropylmethyl-amino-pyrimidin-4yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         trams-isomer, (Compound A208);         {4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetonitrile,         trans-isomer, (Compound A209);         3-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionitrile,         trans-isomer, (Compound A210);         (2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl)-1H-imidazol-2-yl}-[1,3]dioxan-5-yl)-methanol,         trams-isomer, (Compound A211);         (2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl)-1H-imidazol-2-yl}-[1,3]dioxan-5-yl)-methanol,         trams-isomer, (Compound A212);         2-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetamide,         trans-isomer, (Compound A213);         3-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionamide,         trans-isomer, (Compound A214);         {2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl}-[1,3]dioxan-5-yl)-methanol,         trams-isomer, (Compound A215);     -   (k) By proceeding in a similar manner to Example 23 (b) but         using         {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,         cis-isomer, (Compound KO) there are prepared Compounds A171 to         A215.

EXAMPLE 24

Compounds IP to IW

(a) A stirred solution of {2-[4-(4-fluoro-phenyl)-5-(2-methanesulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, trans isomer, (1 equivalent, Compoud KB) and an appropriately substituted alcohol or phenol [5 equivalents, see table 8] in dry dimethylformamide, at room temperature, was treated with sodium hydride [6 equivalents]. After stirring for 16 hours the reaction mixture was evaporated and the reside partitioned between water and ethyl acetate. The organic phase was evaporated to give Compounds IP to IW depicted in Table 8. The R_(F) values indicated in Table 8 were determined using a mixture of ethyl acetate and methanol (9:1, v/v) as eluant [the eluant for Compound IT was a mixture of ethyl acetate and methanol (1:1, v/v)].

TABLE 8 STRUCTURE and MOLECULAR MH⁺ Compound number R¹⁷OH R_(F) FORMULA (Intensity)

0.37 C24H26FN5O5 484 (100%)

0.45 C30H30FN5O5 560 (100%)

0.41 C29H28FN5O5 546 (100%)

0.28 C26H30FN5O6 528 (100%)

0.19 C27H33FN6O5 541 (100%)

0.43 C29H34FN5O5 552 (100%)

0.43 C26H30FN5O5 512 (100%)

(b) By proceeding in the same manner to Example 24 (a) there are prepared Compounds A216 to A219.

-   {2-[4-(4-fluoro-phenyl)-5-(2-hydroxypyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A216); -   {2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A217); -   (2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A218); -   (2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A219);

(c) By proceeding in a similar manner to Example 24 (a) but using 2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5,5-dimethyl-[1,3]dioxane (Compound KI) there were prepared Compounds IY to JE in Table 8a.

TABLE 8a

11.44 C20H21FN4O3 386 (100%)

13.40 C26H25FN4O3 461 (100%)

13.15 C25H23FN4O3 447 (100%)

11.08 C22H25FN4O4 429 (100%)

9.60 C23H28FN5O3 442 (100%)

13.52 C25H29FN4O3 453 (100%)

12.14 C22H25FN4O3 413 (100%)

(d) By proceeding in the same manner to Example 24 (c) there are prepared Compounds A220 to A222.

-   4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-propoxy-pyrimidine,     (Compound A220); -   2-{4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-ethanol,     (Compound A221); -   3-{4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-propan-1-ol,     (Compound A222);

(e) By proceeding in a similar manner to Example 24 (a) but using {2-[5-(2-methanesulphonyl-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol, trans-isomer, (Compound KJ) there are prepared Compounds A223 to A232:

-   {2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     trans-isomers, trans-isomer, (Compound A223); -   {2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound A224); -   {2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound A225); -   (2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-methanol,     trans-isomer, (Compound A226); -   {2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound A227); -   {2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound A228); -   {2-[5-(2-isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound A229); -   {2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound A230); -   2-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-5-methyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-ethanol,     trans-isomer, (Compound A231); -   3-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-5-methyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-propan-1-ol,     trans-isomer, (Compound A232);

(f) By proceeding in a similar manner to Example 24 (e) but using {2-[5-(2-methanesulphonyl-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol, cis-isomer, (Compound KK) there are prepared the corresponding cis-isomers of Compounds A223 to A232.

(g) By proceeding in a similar manner to Example 24 (a) but using {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}methanol, trans-isomer, (Compound KN) there are prepared Compounds A223 to A242:

-   {2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound A233); -   {2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound A234); -   {2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound A235); -   (2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-[1,3]dioxan-5-yl)-methanol,     trans-isomer, (Compound A236); -   {2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound A237); -   {2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound A238); -   {2-[5-(2-isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound A239); -   {2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol,     trans-isomer, (Compound A240); -   2-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-ethanol,     trans-isomer, (Compound A241); -   3-{4-[5-(4-fluoro-phenyl)-2-(5-hydroxymethyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-propan-1-ol,     trans-isomer, (Compound A242);

(h) By proceeding in a similar manner to Example 24 (g) but using {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol, cis-isomer, (Compound KO) there are prepared the corresponding cis-isomers of Compounds A233 to A242.

(i) By proceeding in a similar manner to Example 24 (a) but using 4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-2-methylsulphonyl-pyrimidine (Compound KL) there are prepared Compounds A243 to A252:

-   4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-2-methoxy-pyrimidine,     (Compound A243); -   2-benzyloxy-4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidine,     (Compound A244); -   4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3-H-imidazol-4-yl]-2-phenoxy-pyrimidine,     (Compound A245); -   4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-2-(2-methoxy-ethoxy)-pyrimidine,     (Compound A246); -   (2-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-ethyl)-dimethyl-amine,     (Compound A247); -   2-cyclohexyloxy-4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidine,     (Compound A248); -   2-cyclopropoxy-4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidine,     (Compound A249); -   4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-2-propoxy-pyrimidine,     (Compound A250); -   2-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-ethanol,     (Compound A251); -   3-{4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-propan-1-ol,     (Compound A252);

(j) By proceeding in a similar manner to Example 24 (a) but using 4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-methylsulphonyl-pyrimidine (Compound KM) there are prepared Compounds A253 to A262:

-   4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-methoxy-pyrimidine,     (Compound A253); -   2-benzyloxy-4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidine     (Compound A254); -   4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-phenoxy-pyrimidine,     (Compound A255); -   4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-(2-methoxy-ethoxy)-pyrimidine,     (Compound A256); -   (2-{4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidine-2-yloxy}-ethyl)-dimethyl-amine,     (Compound A257); -   2-cyclohexyloxy-4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidine,     (Compound A258); -   2-isopropyloxy-4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidine,     (Compound A259); -   4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-propoxy-pyrimidine,     (Compound A260); -   2-{4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidine-2-yloxy}-ethanol,     (Compound A261); -   3-{4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidine-2-yloxy}-propan-1-ol,     (Compound A262);

EXAMPLE 25

Compounds JF to KG

(a) A solution of 2,2,2-trifluoro-N-[2-{4-(4-fluoro-phenyl)-5-(2-methanesulphonylpyrimidin-4-yl)-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl]acetamide, cis-isomer, (1 equivalent, Compound KP) and an appropriately substituted amine of formula NHY⁴Y⁵ [5 equivalents, see Table 9] in dry dimethylformamide was heated at 100° C. for 8 hours (or in the case of JF reacted without a solvent in a pressure vessel). The reaction mixture was then treated with aqueous potassium carbonate solution (2 equivalents) and then heated at 100° C. for 24 hours. The mixture was partitioned between water and dichloromethane. The organic phase was separated, evaporated and the residue subjected to high pressure liquid chromatography, on a C18 Dynamax 60 Å column using gradient elution with a mixture of acetonitrile and water as the mobile phase (0-3 minutes 20% acetonitrile; 2-15 minutes ramp up to 80% acetonitrile; 16 minutes to end of run 80% acetonitrile) and UV detection at 254 nm, to give Compounds JF to KG depicted in Table 9. The R_(T) values indicated in Table 9 refer to the high pressure liquid chromatography retention times determined as described above.

TABLE 9 STRUCTURE and R_(T) MOLECULAR MH⁺ EXAMPLE NUMBER HNY⁴Y⁵ (minutes) FORMULA (Intensity)

NH₃ 11.41 C18H19FN6O2 371 (100%)

11.65 C19H21FN6O2 385 (100%)

11.85 C20H23FN6O2 399 (100%)

12.10 C21H23FN6O2 411 (100%)

2.70 C23H28FN7O2 454 (100%)

10.91 C24H29FN6O2 453 (100%)

10.30 C20H23FN6O3 415 (100%)

1.96 C20H24FN7O2 414 (100%)

1.98 C24H27FN8O2 479 (100%)

2.02 C25H32FN7O3 498 (100%)

10.40 C21H25FN6O2 413 (100%)

10.18 C25H25FN6O2 461 (100%)

10.91 C26H27FN6O2 475 (100%)

10.91 C26H27FN6O2 475 (100%)

11.01 C24H23FN6O2 447 (100%)

13.15 C23H27FN6O2 439 (100%)

3.95 C24H24FN7O2 462 (100%)

2.14 C24H24FN7O2 462 (100%)

1.96 C24H24FN7O2 462 (100%)

11.93 C23H23FN6O3 451 (100%)

12.10 C23H23FN6O2S 467 (100%)

12.44 C23H27FN6O3 455 (100%)

2.10 C23H28FN7O2 454 (100%)

12.20 C22H25FN6O3 441 (100%)

11.10 C22H27FN6O3 443 (100%)

11.86 C21H25FN6O3 429 (100%)

2.02 C23H30FN7O2 456 (100%)

2.04 C22H28FN7O2 442 (100%)

(b) By proceeding in the same manner Example 25 (a) there are prepared Compounds A263 to A280.

-   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, cis-isomer, (Compound A263); -   3-{4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, cis-isomer, (Compound A264); -   {4-[2-(5-amino-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-isopropyl-amine,     cis-isomer, (Compound A265); -   allyl-{4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-3-yl]-pyrimidin-2-yl}-amine,     cis-isomer, (Compound A266); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-cyclopropylmethyl-amine,     cis-isomer, (Compound A267); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetonitrile,     cis-isomer, (Compound A268); -   3-{4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionitrile,     cis-isomer, (Compound A269); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-3-yl-amine,     cis-isomer, (Compound A270); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-4-yl-amine,     cis-isomer, (Compound A271); -   2-{4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl}-pyrimidin-2-ylamino]-acetamide,     cis-isomer, (Compound A272); -   3-{4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionamide,     cis-isomer, (Compound A273); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-propyl-amine,     cis-isomer, (Compound A274); -   2-[4-(4-fluoro-phenyl)-5-(2-pyrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylamine,     cis-isomer, (Compound A275); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(4-fluorobenzyl)-amine,     cis-isomer, (Compound A276); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(4-methoxybenzyl)-amine,     cis-isomer, (Compound A277); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(4-fluorophenyl)-amine,     cis-isomer, (Compound A278); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(3,4-difluorophenyl)-amine,     cis-isomer, (Compound A279); -   {4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(4-methoxyphenyl)-amine,     cis-isomer, (Compound A280);

(c) By proceeding in a similar manner to Example 25(a) but replacing the amine with a single equivalent of the sodium salt of an appropriately substituted alcohol or phenol there are prepared Compounds A281 to A290.

-   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylamine,     cis-isomer, (Compound A281); -   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-ylamine,     cis-isomer, (Compound A282); -   2-[2-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-ylamine,     cis-isomer, (Compound A283); -   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylamine,     cis-isomer, (Compound A284); -   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylamine,     cis-isomer, (Compound A285); -   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylamine,     cis-isomer, (Compound A286); -   2-[5-(2-Isolopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylamine,     cis-isomer, (Compound A287); -   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylamine,     cis-isomer, (Compound A288); -   2-{4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-ethanol,     cis-isomer, (Compound A289); -   3-{4-[2-(5-amino-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-propan-1-ol,     cis-isomer, (Compound A290);

(d) By proceeding in a similar manner to Example 25 (a) but using 2,2,2-trifluoro-N-{2-[5-(2-methylsulphonyl-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide, trans isomer (Compound LL) there are prepared. Compounds A291 to A337.

-   4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamine,     trans-isomer, (Compound A291); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-methyl-amine,     trans-isomer, (Compound 292); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-dimethyl-amine,     trans-isomer, (Compound A293); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-cyclopropyl-amine,     trans-isomer, (Compound A294); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-piperidin-4-yl-amine,     trans-isomer, (Compound A295); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-cyclohexyl-amine,     trans-isomer (Compound A296); -   2-[4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino]-ethanol,     trans-isomer, (Compound A297); -   N1-{4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-ethane-1,2-diamine,     trans-isomer, (Compound A298); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-[3-(5H-imidazol-1-yl)-propyl]-amine,     trans-isomer, (Compound A299); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(3-morpholin-4-yl-propyl)-amine,     trans-isomer, (Compound A300); -   3-[4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino]-propan-1-ol,     trans-isomer, (Compound A301); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-benzyl-amine,     trans-isomer, (Compound A302); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(4-fluorobenzyl)-amine,     trans-isomer, (Compound A303); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(4-methoxybenzyl)-amine,     trans-isomer, (Compound A304); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(1-phenyl-ethyl)-amine,     R isomer, trans-isomer, (Compound A305); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(1-phenyl-ethyl)-amine,     S isomer, trans-isomer, (Compound A306); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-phenyl-amine,     trans-isomer, (Compound A307); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(4-fluorophenyl)-amine,     trans-isomer, (Compound A308); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(3,4-difluorophenyl)-amine,     trans-isomer, (Compound A309); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(3-methoxyphenyl)-amine,     trans-isomer, (Compound A310); -   C-{2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methylamine,     trans-isomer, (Compound A311); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxane-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-4-ylmethyl-amine,     trans-isomer, (Compound A312); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-3-ylmethyl-amine,     trans-isomer, (Compound A313); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-2-ylmethyl-amine,     trans-isomer, (Compound A314); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(furan-2-ylmethyl)-amine,     trans-isomer, (Compound A315); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(thiophen-2-ylmethyl)-amine,     trans-isomer, (Compound A316); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(tetrahydro-furan-2-ylmethyl)-amine,     trans-isomer, (Compound A317); -   C-(2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-methylamine,     trans-isomer, (Compound A318); -   C-{2-[4-(4-fluoro-phenyl)-5-(2-morpholino-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3-dioxan]-5-yl}-methylamine     trans-isomer, (Compound A319); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(3-methoxy-propyl)-amine,     trans-isomer, (Compound A320); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-(2-methoxy-ethyl)-amine,     trans-isomer, (Compound A321); -   N-{4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-N′,N′-dimethyl-propane-1,3-diamine,     trans-isomer, (Compound A322); -   N-{4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-N′,N′-dimethyl-ethane-1,2-diamine,     trans-isomer, (Compound A323); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]pyrimidin-2-ylamino}-acetic     acid, trans-isomer, (Compound A324); -   3-{4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]pyrimidin-2-ylamino}-propionic     acid, trans-isomer, (Compound A325); -   C-{2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]-dioxan-5-yl}-methylamine,     trans-isomer, (Compound A326); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-isopropyl-amine,     trans-isomer, (Compound A327); -   allyl-{4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-amine,     trans-isomer, (Compound A328); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-cyclopropylmethyl-amine,     trans-isomer, (Compound A329); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetonitrile,     trans-isomer, (Compound A330); -   3-{4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionitrile,     trans-isomer, (Compound A331); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-pyridin-3-yl-amine,     trans-isomer, (Compound A332); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyramidin-2-yl}-pyridin-4-yl-amine,     trans-isomer, (Compound A333); -   2-{4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetamido,     trans-isomer, (Compound A334); -   3-{4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionamide,     trans-isomer, (Compound A335); -   {4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl}-propyl-amine,     trans-isomer, (Compound A336); -   C-{2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methylamine,     trans-isomer, (Compound A337);

(e) By proceeding in a similar manner to Example 25 (d) but using 2,2,2-trifluoro-N-{2-[5-(2-methylsulphonyl-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide, cis isomer, (Compound LK) there are prepared the corresponding cis isomers of Compounds A291 to A337.

(f) By proceeding in a similar manner to Example 25 (c) but using 2,2,2-trifluoro-N-{2-[5-(2-methylsulphonyl-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide, trans isomer (Compound LL) there are prepared Compounds A338 to A347.

-   C-{2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methylamine,     trans-isomer, (Compound A338); -   C-{2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methylamine,     trans-isomer, (Compound A339); -   C-{2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methylamine,     trans-isomer, (Compound A340); -   C-(2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-methylamine,     trans-isomer, (Compound A341); -   (2-{4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-ethyl)-dimethyl-amine,     trans-isomer, (Compound A342); -   C-{2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methylamine,     trans-isomer, (Compound A343); -   C-{2-[5-(2-isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methylamine,     trans-isomer, (Compound A344); -   C-{2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methylamine,     trans-isomer, (Compound A345); -   2-{4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-ethanol,     trans-isomer, (Compound A346); -   3-{4-[2-(5-aminomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yloxy}-propan-1-ol,     trans-isomer, (Compound A347);

(g) By proceeding in a similar manner to Example 25 (f) but using 2,2,2-trifluoro-N-{2-[5-(2-methylsulphonyl-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide, cis isomer, (Compound LK) there are prepared the corresponding cis isomers of Compounds A338 to A347.

EXAMPLE 26

Compounds A348 to A575

(a) (i) Treatment of C-{2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanyl)-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methylamine, cis-isomer (Compound KZ) with either acetyl chloride, benzoyl chloride, phenylacetyl chloride according to method described in Example 11 or methanesulphonyl chloride according to method described in Example 13;

(ii) Treatment of compounds obtained from (i) with m-chloroperbenzoic acid according to method described for Example 27;

(iii) Treatment of compounds from (iii) with amines of formula HNY⁴Y⁵ or sodium salts of appropriately substituted alcohols or phenols according to methods described in Example 23 or Example 24;

gives compounds A348 to A575:

-   N-{2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A348); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyridin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer (Compound A349); -   N-{2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A350); -   N-{2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A351); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     cis-isomer, (Compound A352); -   N-{2-[5-(2-cyclohexylamino-pyridin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A353); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     cis-isomer, (Compound A354); -   N-{2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A355); -   N-[2-{4-(4-fluoro-phenyl)-5-[2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl]-acetamide,     cis-isomer, (Compound A356); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     cis-isomer, (Compound A357); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     cis-isomer, (Compound A358); -   N-{2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A359); -   N-{2-[5-(2-(4-fluorobenzyl)amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A360); -   N-{2-[5-(2-(4-methoxybenzyl)amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A361); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     R isomer, cis-isomer, (Compound A362); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     S isomer, cis-isomer, (Compound A363); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A364); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-fluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A365); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-(3,4-difluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A366); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-(3-methoxyphenyl)amino-pyridin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A367); -   N-{-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A368); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-acetamide,     cis-isomer, (Compound A369); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-acetamide,     cis-isomer, (Compound A370); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-acetamide,     cis-isomer, (Compound A371); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-acetamide,     cis-isomer, (Compound A372); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-acetamide,     cis-isomer, (Compound A373); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-acetamide,     cis-isomer, (Compound A374); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     cis-isomer, (Compound A375); -   M-{2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A376); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     cis-isomer, (Compound A377); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     cis-isomer, (Compound A378); -   N-{2-[5-[2-(3-dimethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A379); -   N-{2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A380); -   {4-[2-[5-acetylamino-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, cis-isomer, (Compound A381); -   3-{4-[2-[5-(acetylamino-methyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, cis-isomer, (Compound A382); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A383); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetmaide,     cis-isomer, (Compound A384); -   N-{2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A385); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A386); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-5-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     cis-isomer, (Compound A387); -   N-{2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A388); -   N-{2-[5-(2-cyclohexyloxy-pyrimidin-4yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A389); -   N-{2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A390); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A391); -   N-{2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A392); -   N-{2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A393); -   N-{2-[5-[2-(cyclomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A394); -   N-{2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A395); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     cis-isomer, (Compound A396); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     cis-isomer, (Compound A397); -   2-{4-[2-[5-(acetylamino-methyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetamide,     cis-isomer, (Compound A398); -   3-{4-[2-[5-(acetylamino-methyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionamide,     cis-isomer, (Compound A399); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A400); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     cis-isomer, (Compound A401); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-acetamide,     cis-isomer, (Compound A402); -   N-{[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]-dioxan-5-methyl}-acetamide,     cis-isomer, (Compound A403); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide,     cis-isomer, (Compound A404); -   N-{2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A405); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A406); -   N-{2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]-dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A407); -   N-{2-[5-(2-cyanopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A408); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     cis-isomer, (Compound A409); -   N-{2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A410); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     cis-isomer, (Compound A411); -   N-{2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A412); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-methanesulfonamide,     cis-isomer, (Compound A413); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     cis-isomer, (Compound A414); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     cis-isomer, (Compound A415); -   N-{2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A416); -   N-{2-[5-(2-(4-fluorobenzyl)amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A417); -   N-{2-[5-(2-(4-methoxybenzyl)amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A418); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     R isomer, cis-isomer, (Compound A419); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     S isomer, cis-isomer, (Compound A420); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A421); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-(4-fluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A422); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-(3,4-difluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A423); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-(3-methoxyphenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A424); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A425); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-methanesulfonamide,     cis-isomer, (Compound A426); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-methanesulfonamide,     cis-isomer, (Compound A427); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-methanesulfonamide,     cis-isomer, (Compound A487); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-methanesulfonamide,     cis-isomer, (Compound A429); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-methanesulfonamide,     cis-isomer, (Compound A430); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-methanesulfonamide,     cis-isomer, (Compound A431); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     cis-isomer, (Compound A432); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A433); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     cis-isomer, (Compound A434); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     cis-isomer, (Compound A435); -   N-{2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A436); -   N-{2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A437); -   (4-{5-(4-fluoro-phenyl)-2-[5-(methansulfonylamino-methyl)-5-methyl-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetic     acid, cis-isomer, (Compound A438); -   3-(4-{5-(4-fluoro-phenyl)-2-[5-(methanesulfonamide-methyl)-5-methyl-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionic     acid, cis-isomer, (Compound A439); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A440); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A441); -   N-{2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A442); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A443); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     cis-isomer, (Compound A444); -   N-{2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A445); -   N-{2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A446); -   N-{2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A447); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A448); -   N-{2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A449); -   N-{2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A450); -   N-{2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer (Compound A451); -   N-{2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer (Compound A452); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     cis-isomer, (Compound A453); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     cis-isomer, (Compound A454); -   2-(4-{5-(4-fluoro-phenyl)-2-[5-methanesulfonylamino-methyl)-5-methyl-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetamide,     cis-isomer, (Compound A455); -   3-(4-{5-(4-fluoro-phenyl)-2-[5-(methanesulfonylamino-methyl)-5-methyl-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionamide,     cis-isomer, (Compound A456); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A457); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     cis-isomer, (Compound A458); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-methanesulfonamide,     cis-isomer, (Compound A459); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A460); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulfonamide,     cis-isomer, (Compound A461); -   N-{2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A462); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A463); -   N-{2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A464); -   N-{2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A465); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     cis-isomer, (Compound A466); -   N-{2-[5-(cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A467); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     cis-isomer, (Compound A468); -   N-{2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A469); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-benzamide,     cis-isomer, (Compound A470); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     cis-isomer, (Compound A471); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     cis-isomer, (Compound A472); -   N-{2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A473); -   N-{2-[5-(2-(4-fluorobenzyl)amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A474); -   N-{2-[5-(2-(4-methoxybenzyl)amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A475); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     R isomer, cis-isomer, (Compound A476); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     S isomer, cis-isomer, (Compound A477); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A478); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-(4-fluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl]-benzamide,     cis-isomer, (Compound A479); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-(3,4-difluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A480); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-(3-methoxyphenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A481); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl]-benzamide,     cis-isomer, (Compound A482); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-benzamide,     cis-isomer, (Compound A483); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-benzamide,     cis-isomer, (Compound A484); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-benzamide,     cis-isomer, (Compound A485); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-benzamide,     cis-isomer, (Compound A486); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-benzamide,     cis-isomer, (Compound A487); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-benzamide,     cis-isomer, (Compound A488); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     cis-isomer, (Compound A489); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazoli-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A490); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     cis-isomer, (Compound 491); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     cis-isomer, (Compound 492); -   N-{2-[5-[2-(3-dimethylamino-propylaamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl]-benzamide,     cis-isomer, (Compound A493); -   N-{2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A494); -   {4-[2-[5-(benzoylamino-methyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, cis-isomer (Compound A495); -   3-{4-[2-[5-benzoylamino-methyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, cis-isomer, (Compound A496); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A497); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3-dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A498); -   N-{2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl]-benzamide,     cis-isomer, (Compound A499); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A500); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     cis-isomer, (Compound A501); -   N-{2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A502); -   N-{2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A503); -   N-{2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A504); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A505); -   N-{2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A506); -   N-{2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A507); -   N-{2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A508); -   N-{2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A509); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     cis-isomer, (Compound A510); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     cis-isomer, (Compound A511); -   N-{2-[5-[2-(Carbamoylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A512); -   N-{2-[5-[2-(2-Carbamoyl-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A513); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A514); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     cis-isomer, (Compound A515); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-benzamide,     cis-isomer, (Compound A516); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A517); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzamide,     cis-isomer, (Compound A518); -   N-{2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A519); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A520); -   N-{2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A521); -   N-{2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A522); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     cis-isomer, (Compound A523); -   N-{2-[5-(2-cyclohexylamino-pyrimdin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A524); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     cis-isomer, (Compound A525); -   N-{2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl]-2-phenyl-acetamide,     cis-isomer, (Compound A526); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-2-phenyl-acetamide,     cis-isomer, (Compound A527); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     cis-isomer, (Compound A528); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     cis-isomer, (Compound A529); -   N-{2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A530); -   N-{2-[5-(2-(4-fluorobenzyl)amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A531); -   N-{2-[5-(2-(4-methoxybenzyl)amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A532); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     R isomer, cis-isomer, (Compound A533); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     S isomer, cis-isomer, (Compound A534); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A535); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-(4-fluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A536); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-(3,4-difluorophenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A537); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-(3-methoxyphenyl)amino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A538); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A539); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-2-phenyl-acetamide,     cis-isomer, (Compound A540); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-2-phenyl-acetamide,     cis-isomer, (Compound A541); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-2-phenyl-acetamide,     cis-isomer, (Compound A542); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-2-phenyl-acetamide,     cis-isomer, (Compound A543); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-2-phenyl-acetamide,     cis-isomer, (Compound A544); -   N-[2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-ylmethyl]-2-phenyl-acetamide,     cis-isomer, (Compound A545); -   N-(2-[4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     cis-isomer, (Compound A546); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A547); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     cis-isomer, (Compound A548); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     cis-isomer, (Compound A549); -   N-{2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A550); -   N-{2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A551); -   (4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-phenylacetylamino-methyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetic     acid, cis-isomer, (Compound A552); -   3-(4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(phenylacetylamino-methyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionic     acid, cis-isomer, (Compound A553); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A554); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A555); -   N-{2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A556); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A557); -   N-(2-[4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     cis-isomer, (Compound A558); -   N-{2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A559); -   N-{2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A560); -   N-{2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A561); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A562); -   N-{2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A563); -   N-{2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A564); -   N-{2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A565); -   N-{2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A566); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     cis-isomer, (Compound A567); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     cis-isomer, (Compound A568); -   2-(4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(phenylacetylamino-methyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetamide,     cis-isomer, (Compound A569); -   3-(4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(phenylacetylamino-methyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionamide,     cis-isomer, (Compound A570); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A571); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     cis-isomer, (Compound A572); -   N-(2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-3-yl}-5-methyl-[1,3]dioxan-5-ylmethyl)-2-phenyl-acetamide,     cis-isomer, (Compound A573); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A574); -   N-{2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide,     cis-isomer, (Compound A575).     (b) By proceeding in a similar manner to Example 26 (a) but using     C-{2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methylamine,     cis-isomer, there are prepared the corresponding trans-isomers of     Compounds A348 to A575.

EXAMPLE 27

Compounds KH to KP

A suspension of {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, trans isomer, (5.00 g, Compound KQ) in dichloromethane at 0° C. was treated with meta-chloroperbenzoic acid (2 equivalents) and the mixture stirred at 0-5° C. for 2 hours and then at room temperature for a further 16 hours. The reaction mixture was treated with aqueous saturated sodium bicarbonate solution. The organic layer was separated then evaporated. The residue was triturated with ether to give {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, trans isomer, (4.9 g, Compound KH) as a yellow solid, m.p. 264-266° C. MH⁺ 532.

By proceeding in a similar manner but using 2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5,5-dimethyl-[1,3]dioxane (Compound KR) there was prepared 2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5,5-dimethyl-[1,3]dioxane (Compound KJ) as a cream solid, m.p. 204-206° C. MH⁺ 433.

By proceeding in a similar manner but using {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-yl}-methanol, trans-isomer (Compound KU) there is prepared {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-yl}-methanol, trans-isomer (Compound KJ).

By proceeding in a similar manner but using {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-yl}-methanol, cis-isomer (Compound KT) there is prepared {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-yl}-methanol, cis-isomer (Compound KK).

By proceeding in a similar manner but using 2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methylene-[1,3]dioxane (Compound KV) there is prepared 2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methylene-[1,3]dioxane (Compound KL).

By proceeding in a similar manner but using 4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-methylsulphanyl-pyrimidine (Compound KW) there is prepared 4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-methylsulphonyl-pyrimidine (Compound KM).

By proceeding in a similar manner but using {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol, trans-isomer (Compound KX) there is prepared {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol, trans-isomer (Compound KN).

By proceeding in a similar manner but using {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol, cis-isomer (Compound KY) there is prepared {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphonyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol, cis-isomer (Compound KO).

By proceeding in a similar manner but using 2,2,2-trifluoro-N-[2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanylpyrimidin-4-yl)-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl]acetamide, cis-isomer (Compound KQ) there was prepared 2,2,2-trifluoro-N-[2-{4-(4-fluoro-phenyl)-5-(2-methanesulphonylpyrimidin-4-yl)-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl]acetamide, cis-isomer (Compound KP) as a yellow solid, m.p. 236-238° C. MH⁺ 530.

EXAMPLE 28

COMPOUNDS KQ and KY

A solution of 4-[2-dimethoxymethyl-5(4)-(4-fluoro-phenyl)-1H-imidazol-4(5)-yl]-2-methanesulphanyl-pyrimidine (16.0 g, Reference Example 7), p-toluenesulphonic acid (21.13 g), and 3-hydroxy-2-hydroxymethyl-2-methyl-1-morpholino-1-propanone (10.82 g, Reference Example 6) in a mixture of dry tetrahydrofuran and dry dimethylformamide was heated at reflux under a soxhlet apparatus charged with molecular sieves (3 Å) for 26 hours. The reaction mixture was evaporated and the residue treated with ethyl acetate and aqueous saturated sodium bicarbonate solution. The organic phase was evaporated and the residue was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and methanol (9:1, v/v) to give {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, trans isomer, (13.8 g, Compound KQ) as a colourless solid, m.p. 160° C. (with decomposition). MH⁺ 500.

By proceeding in a similar manner but using 2,2-dimethylpropan-1,3-diol there was prepared 2-4-(4-fluoro-phenyl)-5-(2-methylsulphanylpyrimidin-4-yl)-1H-imidazol-2-yl]-5,5-dimethyl-[1,3]dioxane (Compound KR) as a colourless solid, m.p. 163-165° C. (with decomposition). MH⁺ 401.

By proceeding in a similar manner but using 2-methyl-2-trifluoroacetamido-1,3-propanediol (Reference Example 4) there was prepared 2,2,2-trifluoro-N-[2-{4-(4-fluoro-phenyl)-5-(2-methylsulphanyl-pyrimidin-4-yl)-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl]acetamide, cis-isomer, (Compound KS) as a colourless solid. MH⁺ 498. R_(F): 0.55 determined on silica gel plates using a mixture of ethyl acetate and methanol (19:1, v/v).

By proceeding in a similar manner but using 1,1,1-tris(hydroxymethyl)ethane there was prepared {2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol, cis isomer (Compound KT) as white solid [MH⁺ 417. R_(F)=0.32 determined on silica gel plates eluting with a mixture of ethyl acetate and methanol (19:1, v/v)] and {2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol, trans isomer (Compound KU) as a white solid (MH⁺ 417, R_(F)=0.24, determined on silica gel plates eluting with a mixture of ethyl acetate and methanol (19:1, v/v)].

By proceeding in a similar manner but using 2-methylene-1,3-propanediol there is prepared 4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-2-methylsulfanyl-pyrimidine (Compound KV).

By proceeding in a similar manner but using 1,3-propanediol there is prepared 4-[2-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-2-methylsulphanyl-pyrimidine (Compound KW).

By proceeding in a similar manner but using 2-(hydroxymethyl)-1,3-propanediol there is prepared {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol, trans-isomer (Compound KX) and {2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol, cis-isomer (Compound KY).

EXAMPLE 29

COMPOUND KZ

A solution of 2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid amide, cis isomer (0.5 g, Compound LA) in tetrahydrofuran was treated with lithium aluminium hydride (0.18 g) and the mixture heated at reflux for 0.5 hour. To the cooled solution was added water (0.2 ml), then aqueous sodium hydroxide (15%, 0.2 ml) and then water (0.6 ml). The mixture was then filtered and the filtrate was evaporated. The residue was subjected to flash chromatography on silica, eluting with a mixture of methanol and ethyl acetate (3:7, v/v) to give C-{2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methylamine, cis isomer (69 mg, Compound KZ) as a gum. MH⁺ 416. R_(F)=0.3 determined on silica gel plates using methanol.

EXAMPLE 30

COMPOUND LA

To a solution of 2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid, cis isomer (1.3 g, Compound LB), diethyl isopropyl amine (0.85 g) and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (1.14 g) in dimethylformamide (anhydrous) was added ammonia (1.2 mL, 0.5M solution in 1,4-dioxane). The solution was stirred at room temperature for 3 hours and then evaporated. The residue was stirred with water and the solid filtered to give 2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid amide, cis isomer (1.2 g, Compound LA) as white solid. MH⁺ 430. R_(F)=0.27 [determined on silica gel plates using a mixture of ethyl acetate and methanol (8:2 v/v)].

EXAMPLE 31

COMPOUND LB

A solution of 2-[4-(4-fluorophenyl)-5-(2-methylenesulphanylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-carboxylic acid methyl ester, cis isomer, (5.1 g, Compound LD) and aqueous sodium hydroxide (34.4 ml, 1N) in methanol was heated at reflux for 6 hours. To the cold solution was added aqueous hydrochloric acid (34.4 ml, 1N) and the methanol evaporated. The aqueous was decanted and the residue triturated with acetonitrile to give 2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid, cis isomer (4.43 g, Compound LB) as a white solid. MH+ 431. TLC R_(F)=0.22 (eluting with ethyl Acetate and methanol (8:2, v/v) on silica gel).

EXAMPLE 32

COMPOUND LC AND LD

A solution of 2-dimethoxymethyl-4-(4-fluorophenyl)-5-(2-methylsulphanylpyrimidin-4-yl)-1H-imidazole (4.5 g, Reference Example 7), methyl 2,2-bis(hydroxymethyl)propionate (10 g) and methylorthoformate (11.9 ml) in dimethylformamide was treated with 4-toluenesulphonic acid (20.6 g) and then heated at 80° C. for 4 hours. The reaction mixture was evaporated then partitioned between ethyl acetate and aqueous sodium bicarbonate solution. The organic phase was evaporated and the residue purified using flash chromatography on silica gel eluting with a ethyl acetate to give 2-[4-(4-fluorophenyl)-5-(2-methylsulphanylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-carboxylic acid methyl ester, trans isomer, (4.95 g, Compound LC), [MH⁺ 445, m.p. 199-200° C.) and 2-[4-(4-fluorophenyl)-5-(2-methylsulphanylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-carboxylic acid methyl ester, cis isomer (7.11 g, Compound LD), MH⁺ 445, m.p. 161-163° C.).

EXAMPLE 33

COMPOUND LE

To a solution of {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-nitro-[1,3]dioxan-5-yl}-methanol, cis isomer (0.1 g, Compound LG) in ethanol was added palladium on carbon (5%, 0.2 g) and the mixture was hydrogenated at 1 atmosphere of hydrogen at 50° C. for 6 hours. The solution was filtered through Celite, the solvent evaporated and the residue subjected to flash chromatography on silica gel, eluting with a mixture of methanol and ethyl acetate (1:1, v/v) to give {5-Amino-2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol, cis isomer, (77 mg, Compound LE) as a gum. MH⁺ 371. TLC R_(F)=0.27 (eluting with methanol on silica gel).

EXAMPLE 34

COMPOUND LF

To a solution of {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-nitro-[1,3]dioxan-5-yl}-methanol, trans isomer (0.1 g, Compound LH) in ethanol was added palladium on carbon (5%, 0.2 g) and the mixture was hydrogenated, at 1 atmosphere of hydrogen, at 50° C. for 8 hours. The solution was filtered through celite and the solvent was evaporated and the residue subjected to flash chromatography on silica gel, eluting with a mixture of methanol and ethyl acetate (1:1, v/v) to give {5-Amino-2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol, trans isomer, (75 mg, Compound LF) as a gum. MH+ 371. TLC R_(F)=0.19 (eluting with a mixture of ethyl acetate:methanol 1:1 on silica gel).

EXAMPLE 35

COMPOUND LG and LH

A solution of of 4-[2-dimethoxymethyl-5(4)-(4-fluoro-phenyl)-1H-imidazol-4(5)-yl]-pyridine (2.2 g, Reference Example 3), p-toluenesulphonic acid (1.74 g) and tris(hydroxymethyl)-nitromethane (4.24 g) in tetrahydrofuran (anhydrous) and dimethylformamide (anhydrous) was heated at reflux under a soxhlet apparatus charged with molecular sieve (3 Å) for 48 hours. The solvent was evaporated and the residue partitioned between ethyl acetate and aqueous saturated sodium carbonate solution. The organic layer was evaporated and the residue subjected to flash chromatography on silica, eluting with a mixture of methanol and ethyl acetate (1:9, v/v) to give {2-[4-(4-Fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-nitro-[1,3]dioxan-5-yl}-methanol, cis isomer, (0.61 g, Compound LG) as white solid (MH⁺ 401, TLC R_(F)=0.3, eluting with a mixture of Ethyl acetate:Methanol 8:2 on silica gel) and {2-[4-(4-Fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-nitro-[1,3]dioxan-5-yl}-methanol, trans isomer, (0.39 g, Compound LH) as a yellow gum (MH⁺ 401, TLC R_(F)=0.55, eluting with a mixture of ethyl acetate:methanol 8:2 on silica gel).

EXAMPLE 36

COMPOUND LI

To a solution of 4-[2-(5,5-Dimethyl-4-nitromethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine (115 mg, Compound LJ) in methanol was added to a suspension of nickel boride which had been previously prepared by sonication of nickel chloride and sodium borohydride. The mixture was stirred and sodium borohydride (250 mg) added in portions over 1 hour. The reaction mixture was filtered through a thin pad of silica gel and purified using preparative TLC eluting twice with a mixture of dichloromethane, pentane, methanol and ammonia (55:25:18:2, v/v) to give C-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5,5-dimethyl-[1,3]dioxan-4-yl}-methylamine (57 mg, Compound LI). MH⁺ 383. R_(F)=0.54, eluting twice with dichloromethane, pentane, methanol and ammonia (55:25:18:2, v/v).

EXAMPLE 37

COMPOUND LJ

To a solution of 4-[2-dimethoxymethyl-5(4)-(4-fluoro-phenyl)-1H-imidazol-4(5)-yl]-pyridine (115 mg, Reference Example 3) in dry tetrahydrofuran was added 2,2-dimethyl-4-nitrobutane-1,3-diol (150 mg) and p-toluenesulphonic acid. The mixture was heated under reflux for 7 hours before partitioning between water and ethyl acetate and purifying using flash chromatography on silica gel eluting with ethyl acetate:methanol (9:1, v/v) to give 4-[2-(5,5-dimethyl-4-nitromethyl-1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine (130 mg, Compound LJ). MH⁺ 413. TLC R_(F)=0.36 (eluting twice with ethyl acetate: on silica gel).

EXAMPLE 38

COMPOUND LK and LL

(i) Treatment of C-{2-[4-(4-fluoro-phenyl)-5-(2-methylsulphanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methylamine, cis-isomer (Compound KZ) with trifluoroacetic anhydride (according to method described in Example 12); followed by (ii) treatment of compounds obtained from (i) with meta-chloroperbenzoic acid (according to method described for Example 27) gives 2,2,2-trifluoro-N-{2-[5-(2-methylsulphonyl-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide, cis isomer (Compound LK).

By proceeding in a similar manner but using the trans-isomer of Compound KZ there is prepared 2,2,2-trifluoro-N-{2-[5-(2-methylsulphonyl-pyrimdin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-methyl-[1,3]dioxan-5-ylmethyl}-acetamide, trans isomer (Compound LL).

EXAMPLE 39

COMPOUND LM and LN

A solution of 2-[4-(4-fluorophenyl)-5-(2-methylsulphanylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-carboxylic acid methyl ester, trans isomer, (3.15 g, Compound LC) in a mixture of dichloromethane and methanol (9:1, v/v) was treated with 3-chloroperoxybenzoic acid (2.2 equivalents) and stirred at room temperature for 16 hours. The solution was diluted with ether and shaken with aqueous saturated sodium bicarbonate solution. The organic solution was evaporated and the residue triturated with a mixture of ethyl acetate and ether to give 2-[4-(4-fluorophenyl)-5-(2-methylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-carboxylic acid methyl ester, trans isomer (2.95 g, Compound LM) as a colourless crystalline solid, m.p. 186-187° C. MH⁺ 477.

By proceeding in a similar manner but using 2-[4-(4-fluorophenyl)-5-(2-methylsulphanylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-carboxylic acid methyl ester, cis isomer (Compound LD) there is prepared 2-[4-(4-fluorophenyl)-5-(2-methylenesulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-carboxylic acid methyl ester, cis isomer (Compound LN).

EXAMPLE 40

COMPOUND GT and A577 to A2062

(a)

-   -   Step 1: A suspension of Merrifield resin (20 g,         chloromethylpolystyrene resin, Novabiochem) in dimethylformamide         (150 ml) was treated with potassium thioacetate (21 g). After         stirring at room temperature for 24 hours the mixture was         filtered and the modified resin was washed with         dimethylformamide, then with tetrahydrofuran, then with water,         then with tetrahydrofuran, then with dichloromethane and then         dried under high vacuum at 60° C. to give Resin A (20.5 g). IR:         3024s, 2920s, 1691s, 1599m, 1493s, 1453s, 1130m, 738s, 700s.     -   Step 2: A suspension of Resin A from Step 1 (20.5 g) in         tetrahydrofuran (150 ml) was treated with lithium borohydride (5         g). After stirring at room temperature for 24 hours the mixture         was filtered and the modified resin was washed with         tetrahydrofuran, then with a mixture of hydrochloric acid (1N)         and tetrahydrofuran (3:7, v/v), then with water, then with         tetrahydrofuran, then with methanol, then with dichloromethane         and then dried under high vacuum at 60° C. to give Resin B (20         g). IR: 3026 s, 2924s, 1559w, 1493 s, 1452 S, 757 s, 700s.     -   Step 3: A suspension of Resin B from Step 2 (0.1 g) in         dimethylformamide (0.5 ml) was treated with sodium hydride (5         mg, 60% dispersion in mineral oil), then stirred at room         temperature for 15 minutes, then treated with         2-[4-(4-fluorophenyl)-5-(2-methylylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-carboxylic         acid methyl ester, trans isomer, (60 mg, Compound LM) and then         heated at 80° for 20 hours. The reaction mixture was filtered         and the modified resin was washed with dimethylformamide, then         with tetrahydrofuran, then with methanol, then with         dichloromethane and then dried under high vacuum at 60° C. to         give Resin C (0.11 g), IR3021 m, 2920 m, 1732 m, 1569 m, 1487 s,         1452s, 1091 m, 835 m, 757 s, 699 s.     -   Step 4: A suspension of Resin C (0.09 g) in tetrahydrofuran was         treated with aqueous sodium hydroxide solution (1N, 0.3 ml) and         then stirred at 70° C. for 8 hours. The reaction mixture was         filtered and the modified resin was washed with tetrahydrofuran,         then with a mixture of tetrahydrofuran and hydrochloric         acid(1N), then with tetrahydrofuran, then with         dimethylformamide, then with tetrahydrofuran, then with methanol         then with dichloromethane and then dried under high vacuum at         60° C. to give Resin D (0.09 g), IR: 3060w, 3025 m, 2923m, 2852         w, 1720 w, 1601 m, 1571 s, 1493 s, 1452 s, 1335 s, 1235 m, 1199         m, 1183 m, 1097 s, 838 m, 760 s, 704s.     -   Step 5: A suspension of Resin D (0.07 g) in dichloromethane was         treated with oxalyl chloride solution in dichloromethane (16%),         then stirred at room temperature for 10 minutes and then         filtered. This procedure was repeated three times. The modified         resin was washed with dichloromethane, then treated with a         solution of morpholine (0.1 g) in dichloromethane (0.8 ml).         After stirring at room temperature for 10 minutes this reaction         mixture was filtered and the further modified resin was washed         with dichloromethane, then with tetrahydrofuran, then with         methanol, then with dichloromethane and then dried under high         vacuum at 60° C. to give Resin E (0.07 g), IR: 3025s, 2922s,         1636w, 1600w, 1570w, 1493s, 1452s, 1329w, 1181w, 1115w, 759m,         704s.     -   Step 6: A suspension of Resin E (0.06 g) in a mixture of         dichloromethane (0.8 ml) and methanol (0.1 ml) was treated with         m-chloroperoxybenzoic acid (0.24 g). After stirring at room         temperature for 96 hours the reaction mixture was filtered and         the modified resin was washed with dichloromethane, then with         tetrahydrofuran, then with methanol, then with dichloromethane         and then dried under high vacuum at 60° C. to give Resin R (0.06         g). IR: 3082 m, 3026 s, 2927 s, 2851 w, 1635 w, 1602 m, 1582 m,         1493 m, 1452 s, 1350 w, 1240 m, 1180 m, 1117 m, 1032 m, 761s,         705 s.     -   Step 7: A suspension of Resin F (0.04 g) in dimethoxyethane         (0.4 ml) was treated with benzylamine (0.01 ml) and then heated         at 70° C. for 6 hours. The reaction mixture was filtered to         remove resin and the filtrate was evaporated. The residue was         subjected to high pressure liquid chromatography (gradient         elution using water and acetonitrile mixtures as follows: 0-2         minutes 20% acetonitrile, 2-16 minutes ramp up to 80%         acetonitrile) to give the         {2-[4-(4-fluorophenyl-5-(2-benzylaminopyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,         trans isomer (Compound GT). MH⁺ 559. High pressure liquid         chromatography retention time=11 minutes.         (b) By proceeding in a similar manner but using amines of         formula HNY⁴Y⁵ in Step 5; and amines of formula HNY⁴Y⁵ or sodium         salts of appropriately substituted alcohols or phenols in Step 7         there is prepared Compounds A557 to A2062.     -   [5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A577);     -   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A578);     -   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A579);     -   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-5-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A580);     -   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A581);     -   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A582);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A583);     -   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A584);     -   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A585);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A586);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A587);     -   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A588);     -   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, R-isomer, trans-isomer, (Compound A589);     -   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-carboxylic         acid amide, S-isomer, trans-isomer, (Compound A590);     -   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer (Compound A591);     -   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A592);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A593);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A594);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A595);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A596);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5carboxylic         acid amide, trans-isomer, (Compound A597);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound 598);     -   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A599);     -   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyramidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A600);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A601);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A602);     -   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A603);     -   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A604);     -   {4-[2-(5-Carbamoyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic         acid, trans-isomer, (Compound A605);     -   3-{4-[2-(5-Carbamoyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic         acid, trans-isomer, (Compound A606);     -   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A607);     -   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A608);     -   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A609);     -   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A610);     -   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A611);     -   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A612);     -   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A613);     -   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A614);     -   2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A615);     -   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A616);     -   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A617);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A618);     -   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A619);     -   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]-dioxane-5-carboxyic         acid amide, trans-isomer, (Compound A620);     -   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A621);     -   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A622);     -   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A623);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A624);     -   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A625);     -   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A626);     -   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A627);     -   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A628);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A629);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A630);     -   2-[4-(4-fluoro-phenyl)-5-(2-methanesulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid amide, trans-isomer, (Compound A631);     -   2-[5-(2-amino-pyrimidin-4-yl-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A632);     -   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A633);     -   2-[5-(2dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A634);     -   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A635);     -   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A636);     -   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A637);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A638);     -   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A639);     -   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A640);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A641);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A642);     -   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A643);     -   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, R-isomer, trans-isomer, (Compound A644);     -   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, S-isomer, trans-isomer, (Compound A645);     -   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A646);     -   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A647);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A648);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A649);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A650);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A651);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5carboxylic         acid methylamide, trans-isomer, (Compound A652);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyramidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A653);     -   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A654);     -   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A655);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A656);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A657);     -   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A658);     -   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A659;     -   {4-[5-(4-fluoro-phenyl)-2-(5methyl-5-methylcarbamoyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic         acid, trans-isomer, (Compound A660);     -   3-{4-[5-(4-fluoro-phenyl)-2-(5-methyl-5-methylcarbamoyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic         acid, trans-isomer, (Compound A661);     -   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyramidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-4-carboxylic         acid methylamide, trans-isomer, (Compound A622);     -   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A663);     -   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A664);     -   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A665);     -   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A666);     -   2-{4-(4-fluoro-phenyl)-5-[2-pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A667);     -   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A668);     -   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A669);     -   2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, Compound A670);     -   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyramidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A671);     -   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A672);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A673);     -   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A674);     -   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A675);     -   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A676);     -   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A677);     -   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A678);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A679);     -   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A680);     -   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A681);     -   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A682);     -   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A683);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A684);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyramidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A685);     -   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyramidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid methylamide, trans-isomer, (Compound A686);     -   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A687)     -   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A688);     -   2-[2-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A689);     -   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A690);     -   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A691);     -   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A692);     -   2-{5-(4-fluoro-phenyl)-5-[2-hydroxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A693);     -   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer Compound A694);     -   2-{4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A695);     -   2-[4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A696);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A697);     -   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A698);     -   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, R-isomer, trans-isomer, (Compound A699);     -   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, S-isomer, trans-isomer, (Compound A700);     -   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A701);     -   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A702);     -   2-(4-(4-fluoro-phenyl)-5-[2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A703);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A704);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A705);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A706);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound 707);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A708);     -   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A709);     -   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A710);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A711);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A712);     -   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A713);     -   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A714);     -   {4-[2-(5-dimethylcarbamoyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic         acid, trans-isomer, (Compound A 715);     -   3-{4-[2-(5-dimethylcarbamoyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic         acid, trans-isomer, (Compound A716);     -   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A717);     -   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A718);     -   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A719);     -   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A720);     -   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A721);     -   2-{4-(4-fluoro-phenyl)-5-[2-pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (compound A722);     -   2-{4-4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A723);     -   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A724);     -   2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A725);     -   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A726);     -   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A727);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A728);     -   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A729);     -   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A730);     -   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A731);     -   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A732);     -   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A733);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A734);     -   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A735);     -   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A736);     -   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A737);     -   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A738);     -   2-{4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]-dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A739);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A740);     -   2-[4-(4-fluoro-phenyl)-5-(2)methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid dimethylamide, trans-isomer, (Compound A724);     -   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A742);     -   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A743);     -   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A744);     -   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A745);     -   2-{4-(4-fluoro-phenyl)-5-[2-piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A746);     -   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A747);     -   2-[4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A748);     -   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A749);     -   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A750);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A751);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A752);     -   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A753);     -   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, R-isomer, trans-isomer, (Compound A754);     -   2-{4-(4-fluoro-phenyl)-5-[2-(1_phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, S-isomer, trans-isomer, (Compound A755);     -   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A756);     -   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A757);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamino, trans-isomer, (Compound A758);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A759);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A760);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A761);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(thiopheny-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A762);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A763);     -   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A764);     -   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A765);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A766);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A767);     -   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A768);     -   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A769);     -   {4-[2-(5-cyclopropylcarbamoyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic         acid, trans-isomer, (Compound A770);     -   3-{4-[2-(5-cyclopropylcarbamoyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic         acid, trans-isomer, (Compound A771);     -   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A772);     -   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A773);     -   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A774);     -   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H         -imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid         cyclopropylamide, trans-isomer, (Compound A775);     -   2-[5-[2-(2-cyano-ethylamino-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A776);     -   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamino, trans-isomer, (Compound A777);     -   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamino, trans-isomer, (Compound A778);     -   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A779);     -   2-[(4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2yl]-5-methyl-[1,3]dioxane-5-carboxyic         acid cyclopropylamino, trans-isomer, (Compound A780);     -   2-[-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]-dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A781);     -   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]-dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A782);     -   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A783);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A784);     -   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A785);     -   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A786);     -   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A787);     -   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A788);     -   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A789);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A790);     -   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A791);     -   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A792);     -   2-[5-(2-Isopropoxy-pyrimidin-4-yl-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A793);     -   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A794);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A795);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A796);     -   2-[4-(4-fluoro-phenyl)-5-(2-methanesulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid cyclopropylamide, trans-isomer, (Compound A797);     -   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A798);     -   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A799);     -   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A800);     -   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A801);     -   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyramidin-4-yl]-1H-imidazol-2yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A802);     -   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A803);     -   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A804);     -   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A805);     -   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5carboxylic         acid propylamide, trans-isomer, (Compound A806);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A807);     -   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A808);     -   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A809);     -   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, R-isomer, trans-isomer, (Compound A810);     -   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2yl}-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, S-isomer, trans-isomer, (Compound A811);     -   2-[4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A812);     -   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2yl]-5-methyl-[1,3]dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A813);     -   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]-dioxane-5-carboxylic         acid propylamide, trans-isomer, (Compound A814);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A815);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A816);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A817);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A818);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A819);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A820);

-   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A821);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A822);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A823);

-   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A824);

-   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A825);

-   {4-[5-(4-fluoro-phenyl)-2-(5-methyl-5-propylcarbamoyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, trans-isomer, (Compound A826);

-   3-{4-[5-(4-fluoro-phenyl)-2-(5-methyl-5-propylcarbamoyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, trans-isomer, (Compound A827);

-   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A828);

-   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A829);

-   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A830);

-   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A831);

-   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A832);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A833);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A834);

-   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A835);

-   2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A836);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A837);

-   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A838);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A839);

-   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A840);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A841);

-   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A842);

-   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A834);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A844);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A845);

-   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A846);

-   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A847);

-   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A848);

-   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidn-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A849);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A850);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A851);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid propylamide, trans-isomer, (Compound A852);

-   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A853);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A854);

-   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A855);

-   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A856);

-   2-[4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer (Compound A857);

-   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A858);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclhexylamide, trans-isomer, (Compound A859);

-   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A860);

-   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A861);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A862);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A863);

-   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A864);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, R-isomer, trans-isomer, (Compound A865);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, S-isomer, trans-isomer, (Compound A866);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A867);

-   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A868);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A869);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A870);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A871);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A872);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A873);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A874);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A875);

-   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A876);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A877);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A878);

-   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A879);

-   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A880);

-   {4-[2-(5-cyclohexylcarbamoyl-5-methyl-[1,3]dioxane-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, trans-isomer, (Compound A881);

-   3-{4-[2-(5-cyclohexylcarbamoyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, trans-isomer, (Compound A882);

-   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A883);

-   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A884);

-   b     2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A885);

-   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A886);

-   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A887);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A888);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A889);

-   2-[4-(4-fluoro-phenyl)-5(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclhexylamide, trans-isomer, (Compound A890);

-   2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A891);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A892);

-   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer (Compound A893);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A894);

-   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A895);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A896);

-   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A897);

-   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A898);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A899);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A900);

-   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A901);

-   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A902);

-   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A903);

-   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A904);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A905);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A906);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-2H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclohexylamide, trans-isomer, (Compound A907);

-   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A908);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A909);

-   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A910);

-   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A911);

-   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A912);

-   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A913);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A914);

-   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A915);

-   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A916);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A917);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A918);

-   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A919);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, R-isomer, trans-isomer, (Compound     A920);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, S-isomer, trans-isomer, (Compound     A921);

-   2-[4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A922);

-   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A923);

-   2-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A924);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A925);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A926);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A927);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A928);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A929);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A930);

-   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, tans-isomer, (Compound A931);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A932);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A933);

-   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A934);

-   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A935);

-   (4-{5-(4-fluoro-phenyl)-2-[5-(2-hydroxy-ethylcarbamoyl)-5-methyl-[1,3]dioxane-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetic     acid, trans-isomer, (Compound A936);

-   3-(4-{5-(4-fluoro-phenyl)-2-[5-(2-hydroxy-ethylcarbamoyl)-5-methyl-[1,3]dioxane-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionic     acid, trans-isomer, (Compound A937);

-   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A938);

-   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A939);

-   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A940);

-   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A941);

-   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A942);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A943);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A944);

-   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A945);

-   2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A946);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A947);

-   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A948);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A949);

-   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A950);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A951);

-   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A952);

-   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A953);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A954);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A955);

-   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A956);

-   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A957);

-   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A958);

-   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A959);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl)-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A960);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A961);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound A962);

-   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A963);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A964);

-   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A965);

-   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A966);

-   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A967);

-   2-[5-(2-cyanohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A968);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A969);

-   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A970);

-   2-(4-(4-fluoro-phenyl)-5-{2-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A971);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A972);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A973);

-   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A974);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, R-isomer, trans-isomer, (Compound A975);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, S-isomer, trans-isomer, (Compound A976);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A977);

-   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A978);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A979);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A980);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A981);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A982);

-   2-(4-(4-fluoro-phenyl)-5-[2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A983);

-   2-(4-(4fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A984);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A985);

-   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A986);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A987);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A988);

-   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A989);

-   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A990);

-   {4-[2-[5-(2-amino-ethylcarbamoyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, trans-isomer, (Compound A991);

-   3-{4-[2-[5-(2-amino-ethylcarbamoyl)-5-methyl-[1,3dioxane-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, trans-isomer, (Compound A992);

-   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A993);

-   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A994);

-   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A995);

-   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A996);

-   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A997);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A998);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3[dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A999);

-   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1000);

-   2-]4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1001);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1002);

-   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1003);

-   2-{4-     (4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1004);

-   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1005);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1006);

-   2-]4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1007);

-   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1008);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1009);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1010);

-   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1011);

-   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1012);

-   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1013);

-   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidn-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1014);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1015);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1016);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-amino-ethyl)-amide, trans-isomer, (Compound A1017);

-   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1018);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1019);

-   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1020);

-   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1021);

-   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer (Compound A1022);

-   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1023);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1024);

-   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1025);

-   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1026);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1027);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1028);

-   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1029);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, R-isomer, trans-isomer, (Compound     A1030);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, S-isomer, trans-isomer, (Compound     A1031);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1032);

-   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1033);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1034);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1035);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1036);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1037);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1038);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1039);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1040);

-   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1041);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1042);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1043);

-   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1044);

-   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1045);

-   (4-{5-(4-fluoro-phenyl)-2-[5-(3-hydroxy-propylcarbamoyl)-5-methyl-[1,3]dioxane-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetic     acid, trans-isomer, (Compound A1046);

-   3-(4-{5-(4-fluoro-phenyl)-2-[5-(3-hydroxy-propylcarbamoyl)-5-methyl-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionic     acid, trans-isomer (Compound A1047);

-   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1048);

-   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1049);

-   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1050);

-   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1051);

-   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1052);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1053);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1054);

-   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1055);

-   2-{4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1056);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1057);

-   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1058);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1059);

-   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H     -imidazol-2- yl]-5-methyl-[1,3]dioxane-5-carboxylic acid     (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1060);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1061);

-   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1062);

-   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1063);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1064);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1065);

-   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3-]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1066);

-   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1067);

-   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1068);

-   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidn-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1069);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1070);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1071);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound A1072);

-   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide trans-isomer, (Compound A1073);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1074);

-   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1075);

-   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1076);

-   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer (Compound A1077);

-   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1078);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1079);

-   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1080);

-   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1081);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1082);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1083);     2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1084);     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, R-isomer, trans-isomer, (Compound A1085);     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, S-isomer, trans-isomer, (Compound A1086);     2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1087);     2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1088);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmetnyl)-amino]-pyrimidin-4-yl}-1H-imdiazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1089);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1090);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1091);     2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1092);     2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1093);     2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1094);     2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1095);     2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1096);     2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1097);     2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1098);     2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1099);     2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1100); {4-     [2-(5-benzylcarbamoyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, trans-isomer, (Compound A1101);     3-{4-[2-(5-benzylcarbamoyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl}pyrimidin-2-ylamino]-propionic     acid, trans-isomer, (Compound A1102);     2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1103);     2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1104);     2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1105);     2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1106);     2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1107);     2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1108);     2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1109);     2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1110);     2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1111);     2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1112);     2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1113);     2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1114);     2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1115);     2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1116);     2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1117);     2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1118);     2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1119);     2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1120);     2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1121);     2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1122);     2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1123);     2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1124);     2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1125);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1126);     2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1127);     2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid benzylamide, trans-isomer, (Compound A1128);     2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1129);     2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1130);     2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1131);     2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1132);     2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1133);     2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1134);     2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1135);     2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1136);     2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1137);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-yrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1138);     2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1139);     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1140);     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1141);     2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1142);     2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1143);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1144);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1145);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1146);     2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1147);     2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1148);     2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1149);     2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1150);     2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1151);     2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1152);     2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1153);     2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1154);     2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1155);     {4-[5-(4-fluoro-phenyl)-2-(5-methyl-5-phenylcarbamoyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, trans-isomer, (Compound A1156);     3-{4-[5-(4-fluoro-phenyl)-2-(5-methyl-5-phenylcarbamoyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, trans-isomer, (Compound A1157);     2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1158);     2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1159);     2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1160);     2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1161);     2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1162);     2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1163);     2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1164);     2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1165);     2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1166);     2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1167);     2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1168);     2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1169);     2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1170);     2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1171);     2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1172);     2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1173);     2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1174);     2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1175);     2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1176);     2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1177);     2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1178);     2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1179);     2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1180);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1181);     2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid phenylamide, trans-isomer, (Compound A1182);     {2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-yl}piperidin-1-yl-methanone,     trans-isomer, (Compound A1183);     {2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1184);     {2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1185);     {2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1186);     (2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1187);     {2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1188);     (2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1189);     {2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1190);     [2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1191);     (2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1192);     (2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1193);     {2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1194);     (2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     R-isomer, trans-isomer, (Compound A1195);     (2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     S-isomer, trans-isomer, (Compound A1196);     {2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1197);     {2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1198);     [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-piperidin-1-yl-methanone,     trans-isomer, (Compound A1199);     [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-piperidin-1-yl-methanone,     trans-isomer, (Compound A1200);     [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-piperidin-1-yl-methanone,     trans-isomer, (Compound A1201);     [2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1202);     [2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-piperidin-1-yl-methanone,     trans-isomer, (Compound A1203);     [2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1204);     (2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1205);     {2-[4-(4-fluoro-phneyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1206);     (2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1207);     (2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1208);     {2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1209);     {2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1210);     (4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(piperidine-1-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetic     acid, trans-isomer, (Compound A1211);     3-(4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(piperidine-1-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionic     acid, trans-isomer, (Compound A1212);     {2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1213);     {2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1214);     {2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1215);     (4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(piperidine-1-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl]-pyrimidin-2-ylamino)-acetonitrile,     trans-isomer, (Compound A1216);     3-(4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(piperidine-1-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionitrile,     trans-isomer, (Compound A1217);     (2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1218);     (2-{2-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1219);     {2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1220);     {2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1221);     (2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1222);     {2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1223);     (2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1224);     {2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1225);     (2-[4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1226);     {2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1227)     {2-[5-(2-benzyloxy-pyrimidin-2-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1228);     {2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1229);     (2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1230);     {2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1231);     {2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1232);     {2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1233);     {2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1234);     (2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1235);     (2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-piperidin-1-yl-methanone,     trans-isomer, (Compound A1236);     {2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1-yl-methanone,     trans-isomer, (Compound A1237);     2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmetnyl)-amide, trans-isomer, (Compound     A1238);     2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1239);     2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1240);     2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1241);     2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1242);     2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1243);     2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1244);     2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1245);     2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1246);     2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1247);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1248);     2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1249);     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, R-isomer, trans-isomer,     (Compound A1250);     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, S-isomer, trans-isomer,     (Compound A1251);     2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1252);     2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1253);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1254);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1255);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1256);     2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1257);     2-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1258);     2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1259);     2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1260);     2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1261);     2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1262);     2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1263);     2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1264);     2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1265);     [4-(5-(4-fluoro-phenyl)-2-[5-methyl-5-[(tetrahydro-furan-2-ylmethyl)-carbamoyl]-[1,3]dioxan-2-yl}-3H-imidazol-4-yl)-pyrimidin-2-ylamino]-acetic     acid, trans-isomer, (Compound A1266);     3-[4-(5-(4-fluoro-phenyl)-2-{5-methyl-5-[(tetrahydro-furan-2-ylmethyl)-carbamoyl]-[1,3]dioxan-2-yl}-3H-imidazol-4-yl)-pyrimidin-2-ylamino]-propionic     acid, trans-isomer, (Compound A1267);     2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1268);     2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1269);     2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1270);     2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1271);     2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1272);     2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1273);     2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1274);     2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1275);     2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1276);     2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1277);     2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1278);     2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1279);     2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1280);     2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1281);     2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1282);     2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1283);     2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1284);     2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1285);     2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1286);     2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1287);     2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1288);     2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1289);     2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1290);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1291);     2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound     A1292);     {2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1293);     {2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1294);     {2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1295);     {2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1296);     (2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1297);     {2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1298);     (2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1299);     {2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1300);     [2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1301);     (2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1302);     (2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1303);     {2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1304);     (2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1305);     (2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1306);     {2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1307);     {2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1308);     [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl)-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1309);     [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1310);     [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1311);     [2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1312);     [2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1313);     [2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1314);     (2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1315);     {2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1316);     (2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1317);     (2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1318);     {2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1319);     {2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1320);     (4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(4-methyl-piperazine-1-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetic     acid, trans-isomer, (Compound A1321);     3-(4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(4-methyl-piperazine-1-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionic     acid, trans-isomer, (Compound A1322);     {2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1323);     {2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1324);     {2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1325);     (4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(4-methyl-piperazine-1-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetonitrile,     trans-isomer, (Compound A1326);     3-(4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(4-methyl-piperazine-1-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionitrile,     trans-isomer, (Compound A1327);     (2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compund A1328);     (2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(r-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compund A1329);     {2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1330);     {2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1331);     (2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1332);

-   {2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1333);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1334);

-   {2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1335);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1336);

-   {2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1337);

-   {2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1338);

-   {2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1339);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1340);

-   {2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1341);

-   {2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1342);

-   {2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1343);

-   {2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1344);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1345);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1346);

-   {2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone,     trans-isomer, (Compound A1347);

-   {2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1348);

-   {2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1349);

-   {2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1350);

-   {2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1351);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1352);

-   {2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1353);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1354);

-   {2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1355);

-   [2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound A1356);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-mthyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1357);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1358);

-   {2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1359);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     R-isomer, trans-isomer, (Compound A1360);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     S-isomer, trans-isomer, (Compound A1361);

-   {2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1362);

-   {2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1363);

-   [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound A1364);

-   [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound A1365);

-   [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound A1366);

-   [2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound A1367);

-   [2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound A1368);

-   [2-(4-(4-fluoro-phenyl)-5-[2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-morpholin-4-yl-methanone,     trans-isomer, (Compound A1369);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1370);

-   {2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1371);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1372);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1373);

-   {2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1374);

-   {2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1375);

-   (4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(morpholine-4-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetic     acid, trans-isomer, (Compound A1376);

-   3-(4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(morpholine-4-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionic     acid, trans-isomer, (Compound A1377);

-   {2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1378);

-   {2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1379);

-   {2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1380);

-   (4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(morpholine-4-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetonitrile,     trans-isomer, (Compound A1381);

-   3-(4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(morpholine-4-carbonyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionitrile,     trans-isomer, (Compound A1382);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1383);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1384);

-   {2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1385);

-   {2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1386);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1387);

-   {2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1388);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1389);

-   {2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1390);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1391);

-   {2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1392);

-   {2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1393);

-   {2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1394);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1395);

-   {2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1396);

-   {2-[5-(2-cyclyhexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1397);

-   {2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1398);

-   {2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl0[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1399);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1400);

-   (2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-morpholin-4-yl-methanone,     trans-isomer, (Compound A1401);

-   {2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone,     trans-isomer, (Compound A1402);

-   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1403);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1404);

-   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1405);

-   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compount A1406);

-   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1407);

-   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1408);

-   2-{4-(4-(fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1409);

-   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1410);

-   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1411);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-mthoxy-propyl)-amide, trans-isomer, (Compound A1412);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1413);

-   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1414);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, R-isomer, trans-isomer, (Compound     A1415);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, S-isomer, trans-isomer, (Compound     A1416);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1417);

-   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1418);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1419);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-pyropyl)-amide, trans-isomer, (Compound A1420);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1421);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1422);

-   2-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1423);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1424);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1425);

-   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1426);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1427);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1428);

-   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl0[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1429);

-   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1430);

-   (4-{5-(4-fluoro-phenyl)-2-[5-(3-methoxy-propylcarbamoyl)-5-methyl-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetic     acid, trans-isomer, (Compound A1431);

-   3-(4-{5-(4-fluoro-phenyl)-2-[5-(3-methoxy-propylcarbamoyl)-5-methyl-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionic     acid, trans-isomer, (Compound A1432);

-   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1433);

-   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1434);

-   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1435);

-   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1436);

-   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1437);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl--[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1438);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1439);

-   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1440);

-   2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1441);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1442);

-   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1443);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1444);

-   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1445);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1446);

-   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1447);

-   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1448);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1449);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1450);

-   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1451);

-   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1452);

-   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1453);

-   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1454);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1455);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compouns A1456);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-methoxy-propyl)-amide, trans-isomer, (Compound A1457);

-   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1458);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1459);

-   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1460);

-   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1461);

-   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1462);

-   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1463);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1464);

-   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1465);

-   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1466);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1467);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1468);

-   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1469);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, R-isomer, trans-isomer, (Compound     A1470);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, S-isomer, S-isomer, trans-isomer,     (Compound A1471);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1472);

-   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1473);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1474);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1475);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1476);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1477);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1478);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1479);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1480);

-   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1481);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1482);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1483);

-   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1484);

-   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1485);

-   (4-{5-(4-fluoro-phenyl)-2-[5-(2-methoxy-ethylcarbamoyl)-5-methyl-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetic     acid, trans-isomer, (Compound A1486);

-   3-(4-{5-(4-fluoro-phenyl)-2-[5-(2-methoxy-ethylcarbamoyl)-5-methyl-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionic     acid, trans-isomer, (Compound A1487);

-   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1488);

-   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1489);

-   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1490);

-   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1491);

-   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1492);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1493);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1494);

-   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1495);

-   2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1496);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1497);

-   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1498);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1499);

-   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1500);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1501);

-   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1502);

-   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1503);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1504);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1505);

-   2-[5-[2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1506);

-   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1507);

-   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1508);

-   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1509);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1510);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1511);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound A1512);

-   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1513);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1514);

-   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1515);

-   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1516);

-   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1517);

-   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1518);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1519);

-   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1520);

-   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-pyropylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1521);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1522);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1523);

-   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1524);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, R-isomer, trans-isomer,     (Compound A1525);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, S-isomer, trans-isomer,     (Compound A1526);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1527);

-   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboyxlic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1528);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1529);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1530);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1531);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1532);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1533);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1534);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1535);

-   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1536);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1537);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1538);

-   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1539);

-   2-[5-[2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1540);

-   {4-[2-[5-(3-dimethylamino-propylcarbamoyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, trans-isomer, (Compound A1541);

-   3-{4-[2-[5-(3-dimethylamino-propylcarbamoyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, trans-isomer, (Compound A1542);

-   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1543);

-   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1544);

-   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1545);

-   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1546);

-   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1547);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1548);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1549);

-   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1550);

-   2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1551);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1552);

-   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1553);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1554);

-   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1555);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1556);

-   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1557);

-   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1558);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1559);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1560);

-   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1561);

-   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1562);

-   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1563);

-   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1564);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1565);

-   2-[4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-proxy)-pyrimidin-4-yl]-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1566);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound A1567);

-   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1568);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1569);

-   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1570);

-   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1571);

-   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1572);

-   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1573);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1574);

-   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1575);

-   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1576);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1577);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydorxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1578);

-   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1579);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, R-isomer, trans-isomer,     (Compound A1580);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, S-isomer, trans-isomer,     (Compound A1581);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1582);

-   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1583);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1584);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1585);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1586);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1587);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1588);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1589);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1590);

-   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1591);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1592);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1593);     2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1594);     2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)amide, trans-isomer, (Compound A1595);     {4-[2-[5-(2-dimethylamino-ethylcarbamoyl)-5-methyl-[1,3)dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, trans-isomer, (Compound A1596);     3-{4-[2-[5-(2-dimethylamino-ethylcarbamoyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, trans-isomer, (Compound A1597);     2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1598);     2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1599);     2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1600);     2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylaminoethyl)-amide, trans-isomer, (Compound A1601);     2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylaminoethyl)-amide, trans-isomer, (Compound A1602);     2-{4-(4-fluoro-phenyl)-5-(24pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3)dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1603);     2-{4-(4-fluoro-phenyl)-5-[24pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1604);     2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1605);     2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylaminoethyl)-amide, trans-isomer, (Compound A1606);     2-{4-(4-fluoro-phenyl)-5-[2(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1607);     2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5carboxylic     acid (2-dimethylaminoethyl)-amide, trans-isomer, (Compound A1608);     2-{(4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylaminoethyl)-amide, trans-isomer, (Compound A1609);     2-[5-[2(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1610);     2-[4-(4-fluoro-phenyl)-5-[2-(4methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl]-5-methyl-[1,3)dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1611);     2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1612);     2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H     imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid     (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1613);     2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3-dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1614);     2-{4-(4-fluoro-phenyl)-5-[2-(2methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1615);     2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-]1,3)dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1616);     2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl[1,3)dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1617);     2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1618);     2-(4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1619);     2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1620);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl     }-5-methyl-]1,3]dioxane-5-carboxylic acid     (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound A1621);     2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2dimethylamino-ethyl)-amide, trans-isomer, (Compound A1622);     {2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl     }-(3-hydroxy-pyrrolidin-1-yl)-methanone, trans-isomer, (Compound     A1623);     {2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl     }-(3-hydroxy-pyrrolidin-1-yl)-methanone, trans-isomer, (Compound     A1624);     {2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3)dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1625);     {2-[5-(2-cyclopropylamino-pyrimidin-4yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1626);     (2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol     2-yl     }-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1627);     {2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer,(Compound A1628);     (2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl     }-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrimidin-1-yl)-methanone,     trans-isomer, (Compound A1629);     {2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1630);     [2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl)-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1631);     (2-{4-(4-fluoro-phenyl-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl     }-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1632);     (2-{14-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1633);     {2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1634);     (2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     R-isomer, trans-isomer, (Compound A1635);     (2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     S-isomer, trans-isomer, (Compound A1636);     {2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1637);     {2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1638);     [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1639);     [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1640);     [2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(3-hydroxy-pyrrolidin-I-yl)-methanone,     trans-isomer, (Compound A1641);     [2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1642);     [2(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1643);     [2-(4-(4-fluoro-phenyl)-5-(2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl]-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1644);     (2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl}pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1645);     {2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1646);     (2-[4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1647);     (2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1648);     {2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1649);     {2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1650);     (4-{5-(4-fluoro-phenyl)-2-[5-(3-hydroxy-pyrrolidine-1-carbonyl)-5-methyl-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetic     acid, trans-isomer, (Compound A1651);     3-(4-{5-(4-fluoro-phenyl)-2-[5-(3-hydroxy-pyrrolidine-1-carbonyl)-5-methyl-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionic     acid, trans-isomer, (Compound A1652);     {2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1653);     {2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1654);     {2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1655);     (4-{5-(4-fluoro-phenyl)-2-[5-(3-hydroxy-pyrrolidine-1-carbonyl)-5-methyl-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetonitrile,     trans-isomer, (Compound A1656);     3-(4-{5-(4-fluoro-phenyl)-2-[5-(3-hydroxy-pyrrolidine-1-carbonyl)-5-methyl-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionitrile,     trans-isomer, (Compound A1657);     (2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4     -yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1658);     (2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl-methanone,     trans-isomer, (Compound A1659);     {2-{4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1660);     {2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl)-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1661);     (2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1662);     {2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1663);     (2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1664);     {2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1665);     (2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1666);     {2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1667);     {2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1668);     {2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1669);     (2-[4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1670);     {2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1671);     {2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1672);     {2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1673);     {2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1674);     (2-[4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl)-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1675);     (2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1676);     {2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone,     trans-isomer, (Compound A1677);     2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1678);     2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1679);     2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1680);     2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1681);     2-{4-(4-fluoro-phenyl_-5[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1682);     2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1683);     2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1684);     2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1685);     2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1686);     2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1687);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1688);     2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1689);     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl     }-5-methyl-[1,3]dioxane-5-carboxylic acid isopropyl-amide, R-isomer,     trans-isomer, (Compound A1690);     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, S-isomer, trans-isomer, (Compound A1691);     2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1692);     2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1693);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1694);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1695);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1696);     2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1697);     2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1698);     2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1699);     2-{4-(4-fluoro-phenyl)-5-[2-[(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1700);     2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1701);     2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1702);     2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1703);     2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1704);     2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1705);     {4-[5-(4-fluoro-phenyl)-2-(5-isopropylcarbamoyl-5-methyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, trans-isomer, (Compound A1706);     3-{4-[5-(4-fluoro-phenyl)-2-(5-isopropylcarbamoyl-5-methyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, trans-isomer, (Compound A1707);     2[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1708);     2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1709);     2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1710);     2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1711);     2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1712);     2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1713);     2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1714);     2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1715);     2-[4-{4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1716);     2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1717);     2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid, isopropyl-amide, trans-isomer, (Compound A1718);     2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1719);     2-[5-[2(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1720);     2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1721);     2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1722);     2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1723);     2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1724);     2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1725);     2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1726);     2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1727);     2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1728);     2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1729);     2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1730);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1731);     2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid isopropyl-amide, trans-isomer, (Compound A1732);     2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1733);     2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1734);     2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1735);     2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1736);     2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1737);     2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1738);     2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1739);     2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1740);     2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino)-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1741);     2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl     )-5-methyl-[1,3]dioxane-5-carboxylic acid allylamide, trans-isomer,     (Compound A1742);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1743);     2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1744);     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, R-isomer, trans-isomer, (Compound A1745);     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, S-isomer, trans-isomer, (Compound A1746);     2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1747);     2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1748);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1749);     2(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1750);     2(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1751);     2(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1752);     2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1753);     2(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1754);     2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperidin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1755);     2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1756);     2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1757);     2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1758);     2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1759);     2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1760);     {4-[2-(5-allylcarbamoyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, trans-isomer, (Compound A1761);     3-{4-[2-(5-allylcarbamoyl-5-methyl-[1,3]dioxan-2-yl)-5(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, trans-isomer, (Compound A1762);     2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1763);     2-[5-(2-allylamino-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1764);     2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1765);     2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1766);     2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1767);     2-}4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1768);     2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1769);     2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1770);     2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl.     [1,3]dioxane-5-carboxylic acid allylamide, trans-isomer, (Compound     A1771);     2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1772);     2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1773);     2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl[-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1774);     2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1775);     2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1776);     2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1777);     2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1778);     2-(4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1779);     2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A 1780);     2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1781);     2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1782);     2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1783);     2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1784);     2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1785);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1786);     2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid allylamide, trans-isomer, (Compound A1787);     2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1788);     2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1789);     2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1790);     2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1791);     2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1792);     2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1793);     2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1794);     2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1795);     2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1796);     2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1797);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1798);     2-[5-(2-benzylamino-pyrimidin-4-yl)-({4-fluoro-phenyl)1     H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid     cyclopropylmethyl-amide, trans-isomer, (Compound A1799);     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl     }-5-methyl-[1,3]dioxane-5-carboxylic acid cyclopropylmethyl-amide,     R-isomer, trans-isomer, (Compound A1800)     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, S-isomer, trans-isomer, (Compound     A1801)     2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1802);     2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1803);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1804);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1805);     2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1806);     2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol     2-yl)-5-methyl-[1,3]dioxane-5-carboxylic acid     cyclopropylmethyl-amide, trans-isomer, (Compound A1807);     2(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1808);     2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1809);     2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl     )-5-methyl-[1,3]dioxane-5-carboxylic acid cyclopropylmethyl-amide,     trans-isomer, (Compound A1810);     2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1811);     2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1812);     2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1813);     2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1814);     2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1815);     {4-[2-[5-(cyclopropylmethyl-carbamoyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, trans-isomer, (Compound A1816);     3-{4-[2-[5-(cyclopropylmethyl-carbamoyl-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, trans-isomer, (Compound A1817);     2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3)dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A-1818);     2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1819);     2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1820);     2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1821);     2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1822);     2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3)dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1823);     2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino}pyrimidin-4-yl}-1H-imidazol-2-yl]-5-methyl-[1,3)dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1824);     2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1825);     2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1826);     2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1827);     2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-y[-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1823);     2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1829);     2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1830);     2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1831);     2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1832);     2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1833);     2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1834);     2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1835);     2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1836);     2-[5-{2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3)dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1837);     2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1838);     2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1839);     2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A 1840);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1841);     2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyclopropylmethyl-amide, trans-isomer, (Compound A1842);     2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1843);     2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1844);     2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1845);     2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1846);     2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl     ]-5-methyl-[1,3]dioxane-5-carboxylic acid cyanomethyl-amide,     trans-isomer, (Compound A1847);     2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1848);     2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1849);     2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1850);     2-(4-(4-fluoro-phenyl)-5-{2-(3(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl     ]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic acid     cyanomethyl-amide, trans-isomer, (Compound A1851);     2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino]-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1852);     2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1853);     2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1854);     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, R-isomer, trans-isomer, (Compound A1855);     2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, S-isomer, trans-isomer, (Compound A1856);     2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1857);     2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1858);     2(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl)-1H-imidazol-2-yl)-5-methyl-[1,3)dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1859);     2(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1860);     2(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3)dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1861);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1862);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1863);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1864);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1865);

-   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1866);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1867);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1868);

-   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1869);

-   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1870);

-   {4-[2-[5-(cyanomethyl-carbamoyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino-}-acetic     acid, trans-isomer, (Compound A1871);

-   3-{4-[2-[5-(cyanomethyl-carbamoyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, trans-isomer, (Compound A1872);

-   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1873);

-   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1874);

-   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1875);

-   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1876);

-   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1877);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1878);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1879);

-   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1880);

-   2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1881);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1882);

-   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1883);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1884);

-   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1885);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1886);

-   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1887);

-   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1888);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1889);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1890);

-   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1891);

-   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1892);

-   5-carboxylic acid cyanomethyl-amide, trans-isomer, (Compound A1892);

-   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1893);

-   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1894);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1895);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1896);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid cyanomethyl-amide, trans-isomer, (Compound A1897);

-   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1898);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1899);

-   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1900);

-   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1901);

-   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1902);

-   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1903);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1904);

-   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1905);

-   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1906);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1907);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1908);

-   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1909);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, R-isomer, trans-isomer, (Compound     A1910);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, S-isomer, trans-isomer, (Compound     A1911);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1912);

-   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1913);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1914);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1915);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1916);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1917);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1918);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1919);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1920);

-   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1921);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1922);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1923);

-   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1924);

-   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1925);

-   {4-[2-[5-(2-cyano-ethylcarbamoyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-acetic     acid, trans-isomer, (Compound A1926);

-   3-{4-[2-[5-(2-cyano-ethylcarbamoyl)-5-methyl-[1,3]dioxan-2-yl]-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamino}-propionic     acid, trans-isomer, (Compound A1927);

-   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1928);

-   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1929);

-   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1930);

-   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1931);

-   2-[5-[2-(cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1932);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1933);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1934);

-   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1935);

-   2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1936);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1937);

-   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1938);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1939);

-   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1940);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1941);

-   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1942);

-   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1943);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1944);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1945);

-   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1946);

-   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1947);

-   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1948);

-   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1949);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1950);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1951);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid (2-cyano-ethyl)-amide, trans-isomer, (Compound A1952);

-   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1953);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1954);

-   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1955);

-   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1956);

-   2-{4-(4-fluoro-phenyl)-5-[2-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1957);

-   2-{5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1958);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1959);

-   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1960);

-   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1961);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1962);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1963);

-   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1964);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, R-isomer, trans-isomer, (Compound A1965);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, S-isomer, trans-isomer, (Compound A1966);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1967);

-   2-[4-(4-fluoro-phenyl)-5-(2-piperidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1968);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1969);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1970);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1971);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1972);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1973);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1974);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1975);

-   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1976);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1977);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl)-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1978);

-   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1979);

-   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1980);

-   (4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(pyridin-3-ylcarbamoyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetic     acid, trans-isomer, (Compound A1981);

-   3-(4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(pyridin-3-ylcarbamoyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionic     acid, trans-isomer, (Compound A1982);

-   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1983);

-   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1984);

-   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1985);

-   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1986);

-   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1987);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1988);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1989);

-   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1990);

-   2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1991);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1992);

-   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1993);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1994);

-   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1995);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1996);

-   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1997);

-   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1998);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A1999);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A2000);

-   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A2001);

-   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A2002);

-   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A2003);

-   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A2004);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A2005);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A2006);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-3-ylamide, trans-isomer, (Compound A2007);

-   2-[5-(2-amino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2008);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2009);

-   2-[5-(2-dimethylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2010);

-   2-[5-(2-cyclopropylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2011);

-   2-{4-(4-fluoro-phenyl)-5-[2-piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2012);

-   2-[5-(2-cyclohexylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2013);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethylamino-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2014);

-   2-[5-[2-(2-amino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2015);

-   2-(4-(4-fluoro-phenyl)-5-{2-[3-(5H-imidazol-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2016);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2017);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2018);

-   2-[5-(2-benzylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2019);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, R-isomer, trans-isomer, (Compound A2020);

-   2-{4-(4-fluoro-phenyl)-5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, S-isomer, trans-isomer, (Compound A2021);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, R-isomer, trans-isomer, (Compound A2022);

-   2-[4-(4-fluoro-phenyl)-5-(2-piperidinyl-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, S-isomer, trans-isomer, (Compound A2023);

-   2-(4-(4-fluoro-phenyl)-5-{(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2024);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2025);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2026);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide     2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, S-isomer, trans-isomer, (Compound A2027);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2028);

-   2-(4-(4-fluoro-phenyl)-5-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-yl)-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2029);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2030);

-   2-[4-(4-fluoro-phenyl)-5-(2-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2031);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2032);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2033);

-   2-[5-[2-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2034);

-   2-[5-[2-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2035);

-   (4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(pyridin-4-ylcarbamoyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-acetic     acid, trans-isomer, (Compound A2036);

-   3-(4-{5-(4-fluoro-phenyl)-2-[5-methyl-5-(pyridin-4-ylcarbamoyl)-[1,3]dioxan-2-yl]-3H-imidazol-4-yl}-pyrimidin-2-ylamino)-propionic     acid, trans-isomer, (Compound A2037);

-   2-[4-(4-fluoro-phenyl)-5-(2-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2038);

-   2-[5-(2-allylamino-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2039);

-   2-[5-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2040);

-   2-[5-[2-(cyanomethyl-amino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2041);

-   2-[5-[2-(2-cyano-ethylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2042);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2043);

-   2-{4-(4-fluoro-phenyl)-5-[2-(pyridin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2044);

-   2-[4-(4-fluoro-phenyl)-5-(2-propylamino-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2045);

-   2-[4-(4-fluoro-phenyl)-5-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2046);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2047);

-   2-[5-[2-(3,4-difluoro-phenylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2048);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-methoxy-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2049);

-   2-[5-[2-(4-fluoro-benzylamino)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2050);

-   2-{4-(4-fluoro-phenyl)-5-[2-(4-methoxy-benzylamino)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2051);

-   2-[4-(4-fluoro-phenyl)-5-(2-methoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2052);

-   2-[5-(2-benzyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2053);

-   2-[4-(4-fluoro-phenyl)-5-(2-phenoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2054);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-methoxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2055);

-   2-[5-[2-(2-dimethylamino-ethoxy)-pyrimidin-4-yl]-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2056);

-   2-[5-(2-cyclohexyloxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2057);

-   2-[5-(2-Isopropoxy-pyrimidin-4-yl)-4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2058);

-   2-[4-(4-fluoro-phenyl)-5-(2-propoxy-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2059);

-   2-{4-(4-fluoro-phenyl)-5-[2-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2060);

-   2-{4-(4-fluoro-phenyl)-5-[2-(3-hydroxy-propoxy)-pyrimidin-4-yl]-1H-imidazol-2-yl}-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2061);

-   2-[4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic     acid pyridin-4-ylamide, trans-isomer, (Compound A2062);     (c) By proceeding in a similar manner to Example 40 (b) but using     2-[4-(4-fluorophenyl)-5-(2-methylylsulphonylpyrimidin-4-yl)-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-carboxylic     acid methyl ester, cis isomer (Compound LN) there is prepared the     corresponding cis-isomers of Compound GT and Compounds A557 to     A2062.

REFERENCE EXAMPLE 1

4-[5-(4-Fluoro-phenyl)-2-formyl-1-[(2-trimethylsilyl)ethoxy)methyl]-1H-imidazol-4-yl]-pyridine

A solution of 4-[5-(4-fluoro-phenyl)-1-[(2-(trimethylsilyl)ethoxy)methyl]-1H-imidazol-4-yl]-pyridine (8.15 g, reference Example 2) in tetrahydrofuran (100 ml) was treated with a solution of n-butyllithium in hexane (10.6 ml, 2.1M) to give a dark green solution. The solution was stirred at −78° C. for 15 minutes then treated with a solution on N-formylmorpholine (2.45 ml) in tetrahydrofuran (10 ml). After stirring for 15 minutes at −78° C., the mixture was allowed to warm to room temperature then stirred at this temperature for a further 1 hour. The reaction mixture was quenched with water (50 ml) and then extracted four times with ethyl acetate (50 ml). The combined extracts were dried over magnesium sulphate and evaporated. The residual oil was subjected to flash chromatography on silica, eluting with ethyl acetate, to give the title compound (7.86 g) as a yellow oil.

REFERENCE EXAMPLE 2

4-[5-(4-Fluoro-phenyl)-1-[(2-(trimethylsilyl)ethoxy)methyl]-1H-imidazol-4-yl]-pyridine

A stirred solution of 5-(4-fluoro-phenyl)-4-(4-pyridyl)-imidazole [BOEHM ET AL.,] (12.86 g, prepared according to the procedure of Boehm et. al., J. Med. Chem., 1996, 39, page 3829-3937) in dry dimethylformamide (150 ml) was treated portionwise with sodium hydride (2.58 g, 60% dispersion in mineral oil). The mixture was stirred at room temperature until the evolution of hydrogen stopped, then treated dropwise with 2-(trimethylsilyl)ethoxymethyl chloride (10.66 ml). After stirring at room temperature for 1.5 hours, the reaction mixture was treated with water (10 ml) then evaporated. The residual oil was then partitioned between ethyl acetate and water (100 ml). The aqueous phase was extracted three times with ethyl acetate (100 ml). The combined organic phases were washed with brine (50 ml), then dried over magnesium sulphate, then evaporated. The residual yellow oil was subjected to flash chromatography on silica eluting with a mixture of methanol and dichloromethane (98:2, v/v) to give the title compound.

REFERENCE EXAMPLE 3

4-[2-Dimethoxymethyl-5-(4-fluoro-phenyl)-1H-imidazol-4-yl]-pyridine

Method A: A solution of 4-[2-formyl-5-(4-fluoro-phenyl)-1-{(2-trimethylsilyl)ethoxy)-methyl}-1H-imidazol-4-yl]-pyridine (0.525 g, Reference Example 1) in methanol (10 ml) was treated with trimethylorthoformate (5 ml) then with 4-toluenesulphonic acid (0.39 g). The reaction mixture was refluxed for 5 hours, then cooled to room temperature, then evaporated. The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution (30 ml). The aqueous phase was extracted four times with ethyl acetate (20 ml). The combined organic phases were washed with water (15 ml), then with brine (15 ml), then dried over magnesium sulphate and then evaporated. The residual oil was subjected to flash chromatography on silica eluting with a mixture of dichloromethane and methanol (8:1, v/v) to give the title compound (0.344 g) as a white solid, m.p. 186-189° C.

Method B: A stirred suspension of 1-(4-fluorophenyl)-2-(4-pyridyl)-1,2-ethandione (162.74 g, Reference Example 10) in tert-butylmethyl ether (735 ml), at 20-25° C., was treated with a solution of glyoxal 1,1-dimethylacetal in tert-butylmethyl ether (244.4 ml, 45%) followed by a solution of ammonium acetate (140.75 g) in methanol (260 ml) over a period of 30 minutes, during which time the suspension dissolved to form an orange solution. After stirring for 1 hour at 20-25° C., the resulting suspension was cooled to 5-10° C., then stirred for a further 1 hour, then filtered. The damp filter cake was slurry washed three times with water (350 ml) and then the pressed cake washed twice with tert-butylmethyl ether (350 ml). The air-dry cake was then dried in vacuo at 60-65° C. for 16 hours, to afford the title compound, as a cream coloured, free-flowing solid, m.p. 204-206° C. ¹H NMR [δ, (CD₃)₂SO]: 8.35 (d, 2H); 7.43 (dt, 2H); 7.36 (d, 2H); 7.19 (dt, 2H); 5.39 (s, 1H); 3.34 (s, 6H).

REFERENCE EXAMPLE 4

2-Methyl-2-trifluoroacetamido-1,3-propanediol

A stirred solution of 2-amino-2-methyl-1,3-propanediol (1.05 g) in dry dimethylformamide (20 ml), at room temperature, was treated with potassium carbonate (1.52 g). After stirring at room temperature for 15 minutes the mixture was treated dropwise with trifluoroacetic anhydride (1.55 ml) and stirring was then continued for a further 18 hours. The reaction mixture was evaporated and the residue was subjected to flash chromatography on silica eluting with a mixture of dichloromethane and methanol (95:5, v/v) to give the title compound (1 g) as a white solid.

REFERENCE EXAMPLE 5

2-Azidomethyl-2-methyl-1,3-propanediol

A mixture of 5-azidomethyl-2dimethyl-5-methyl-1,3-dioxane [1.48 g, prepared according to the procedure in J. Org. Chem., 1992, page 6080] concentrated hydrochloric acid (0.3 ml), water (0.8 ml) and tetrahydrofuran (10 ml) was heated at reflux for 1 hour. After cooling to room temperature the reaction mixture was evaporated. The residue was dried under vacuum to give the title compound (1.3 g) as a colourless oil.

REFERENCE EXAMPLE 6 3-Hydroxy-2-hydroxymethyl-2-methyl-1-morpholino-1-propanone

A stirred mixture of diisopropylethylamine (339.67 ml) and morpholine (141.71 ml) in acetonitrile (500 ml), at 20-25° C., was treated with 2,2-bis(hydroxymethyl)propionic acid (87.18 g) and 1-hydroxybenzotriazole (43.92 g). The resulting suspension was warmed to 55-60° C. then treated dropwise with a solution of 1,3-dicyclohexylcarbodiimide (147.62 g) in acetonitrile (232.2 ml) over 30 minutes. The resulting solution was then stirred at 55-60° C. for a further 2 hours then filtered to remove the dicyclohexylurea (131.88 g) by-product. The filter cake was washed twice with acetonitrile (250 ml). The filtrate was evaporated and the residue was treated with warm ethyl acetate (500 ml). The resultant solution was allowed to cool for 16 hours then the 1-hydroxybenzotriazole (42.04 g) which crystallised was removed by filtration. Further cooling of the filtrate over 5 hours and filtration gave the title compound (44.82 g), m.p. 95-97° C.

¹H NMR (d, CDCl₃): 4.02 (d, 2H); 3.70 (m, 10H); 3.30 (bs, 2H); 1.08 (s, 3H).

A further quantity of the title compound (41.33 g) was obtained following evaporation of the filtrate from the first crop of product, then treating the residue with ethyl acetate (1000 ml), then passing the solution through a silica gel pad (4 cm high×11 cm diameter), then evaporating the filtrate and then crystallising the residue from n-butyl acetate (1000 ml) over 16 hours.

REFERENCE EXAMPLE 7

4-[2-Dimethoxymethyl-5(4)-(4-fluoro-phenyl)-1H-imidazol-4(5)-yl]-2-methanesulphanyl-pyrimidine

A solution of 1-(4-fluorophenyl)-2-(2-methylsulphanylpyrimidin-4-yl)-1,2-ethandione (18.7 g, Reference Example 8) in t-butyl methyl ether (75 ml) and glyoxal dimethylacetal in t-butylmethyl ether (36 ml, 40%), at room temperature, was treated dropwise over 30 minutes with a solution of ammonium acetate (21.7 g) in methanol (40 ml) to give an orange solution. After stirring for 2 hours at room temperature the resulting suspension was filtered to give the title compound (15.6 g) as a colourless solid, m.p. 180-182° C. MH⁺ 361.

REFERENCE EXAMPLE 8 1-(4-Fluorophenyl)-2-(2-methylsulphanylpyrimidin-4-yl)-1,2-ethandione

A solution of 1-(4-fluorophenyl)-2-(2-methylsulphanylpyrimidin-4-yl)-1-ethanone (65.5 g, Reference Example 9) in dimethylsulphoxide, at 55-70° C., was treated dropwise with an aqueous solution of hydrogen bromide (48%). After stirring at 60° C. for 3 hours, the reaction mixture was cooled to room temperature, then poured into water and the pH of the mixture adjusted to pH8 by addition of sodium bicarbonate. The reaction mixture was extracted with ethyl acetate and the extracts were evaporated to give the title compound (40.87 g), m.p. 74-76° C. MH⁺ 277.

REFERENCE EXAMPLE 9

1-(4-Fluorophenyl)-2-(2-methylsulphanylpyrimidin-4-yl)-1-ethanone

A solution of lithium hexamethyldisilazane in tetrahydrofuran (1.221, 1M), at −40° C., was treated with a solution of 4-methyl-2-methylsulphanylpyrimidine (76.03 g) in tetrahydrofuran (100 ml). The solution was warmed to 0° C., then stirred for 15 minutes, then cooled to −40° C., then treated with a solution of ethyl 4-fluorobenzoate (91.32 g) in tetrahydrofuran (200 ml). After stirring at −40° C. for 15 minutes the reaction mixture was allowed to warm to room temperature over 2 hours, then treated with ammonium chloride solution. The organic phase was separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were evaporated to give the title compound (136.19 g), m.p. 212-214° C. MH⁺ 263.

REFERENCE EXAMPLE 10

1-(4-fluorophenyl)-2-(4-pyridyl)-1,2-ethandione

A mixture of 1-(4-fluorophenyl)-2-(4-pyridyl)-1-ethanone (247.69 g, Reference Example 11) was mixed with dimethylsulfoxide (500 ml) then warmed on a rotary evaporator (no vacuum). The resulting solution was transferred to a reaction vessel with two rinses of dimethylsulfoxide (500 ml and 240 ml) incorporated to ensure complete transfer. The resulting solution was then warmed to 55-65° C. and hydrogen bromide (581.47 g) was added at such a rate so as to maintain the solution temperature in the range 55-65° C., without the need for any external heating. The solution was stirred at 55-65° C. for a further 2 hours, when thin layer chromatography on silica indicated the reaction to be complete. The reaction mixture was added to water (4000 ml) a separate vessel, with external cooling to maintain a solution temperature in the range 15-25° C. The residual contents of the reaction vessel were transferred using a further aliquot of water (2000 ml). The aqueous solution was then treated with a solution of sodium acetate (600 g) in water (2000 ml), over 15 minutes, and the resulting suspension was stirred for 2 hours at ambient temperature, then filtered. The filter cake was washed three times with water (500 ml), then air-dried for 1 hour, then dried in vacuo for 16 hours at 15-25° C. to give the title compound (296.93 g) as a free-flowing yellow-orange powder, m.p. 84-86° C. ¹H NMR (CDCl₃): δ8.81 (d, 2H); 7.98 (dd, 2H), 7.74 (d, 2H); 7.18 (t, 2H).

REFERENCE EXAMPLE 11

1-(4-fluorophenyl)-2-(4-pyridyl)-ethanone

A stirred solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (720 ml, 2M), under nitrogen was treated with 4-picoline (64.7 ml). After 5 minutes a solution of ethyl 4-fluorobenzoate (111.7 g) was added over 30 minutes whilst maintaining the temperature at 18-20° C. by occasional cooling. After stirring at 20-21° C. for 30 minutes, the resultant slurry was cooled in an ice-bath then treated with toluene (500 ml). When the temperature reached 15° C. a solution of acetic acid (82 ml) in water (300 ml) was added over 15 minutes maintaining the temperature below 25° C. After a further 30 minutes stirring at 20-25° C., the organic phase was separated and then evaporated. The oily residue was triturated with heptane to give the title compound (133 g) as a yellow solid, m.p. 80-84° C. ¹H NMR (δ, CDCl₃): 8.42 (d, 2H); 7.88 (dd, 2H); 7.06 (d, 2H); 7.01 (t, 2H); 4.12 (s, 2H).

IN VITRO AND IN VIVO TEST PROCEDURES

1. In Vitro Inhibitory Effects on TNF-alpha Release by Human Monocytes

The effects of compounds on TNF-alpha production by human peripheral blood monocytes (PBMs) are examined as follows.

1.1 Preparation of Human Peripheral Blood Monocytes

Freshly drawn blood from normal healthy donors was missed (4:1, v/v) with sodium citrate (3.8%, w/v). Mononuclear cells were prepared by centrifugation of the blood on Histopaque-1077 (Sigma Diagnostics) according to manufacturers instructions. The fraction enriched with mononuclear cells was washed and resuspended in Hank's balanced salts solution (HBSS) supplemented with deoxyribonuclease (37.5 U/ml) and human serum albumin (0.3%). Differential (cytospin) cell counts revealed that the mononuclear cell fraction routinely comprised 70-80% monocytes.

Cells from the mononuclear leukocyte fraction were centrifuged (200 g, 10 min., 20° C.), resuspended, at a density of 10⁶ cells/ml, in RPMI 1640 containing foetal calf serum (FCS) (1%), penicillin (50 U/ml) and streptomycin (50 μg/ml) and allowed to adhere in 96 well plates. Following incubation (5% CO₂, 37° C.) for 90 min, medium containing non-adherent cells was removed, the cells were washed once with fresh medium and fresh medium was added.

1.2. Measurement of monocyte TNF-alpha release

Adherent cells in culture medium were incubated for 1 h (5% CO₂, 37° C.) with fresh medium containing compounds or vehicle (0.1% dimethylsulphoxide). Compounds were tested within the concentration range of 3×10⁻⁹ M to 3×10⁻M, LPS (10 ng/ml) was then added to the cells and the incubation continued for a further 18 hours. Cell supernatants were removed into 96 well, 0.22 μm filtration plates for storage at −20° C.

TNF-alpha concentrations in cell supernatants were quantified by sandwich ELISA. Briefly ELISA plates were coated overnight with 2 μg/ml of mouse anti-human TNF-alpha antibody in bicarbonate buffer (pH 9.9). After washing the wells with wash buffer (0.05% (v/v) Tween in PBS), and blocking unoccupied sites (1% BSA in PBS), monocyte supernatant samples or human recombinant TNF-alpha standard were vacuum filtered into the corresponding wells of the ELISA plate. Biotinylated rabbit polyclonal anti-human TNF-alpha antibody (3 μg/ml) was used as the second antibody and streptavidin-horseradish peroxidase was used as the detection antibody. The peroxidase substrate was 3,3′,5,5′-tetramethylbenzidine (TMB), in the presence of hydrogen peroxide.

TNFα concentrations in supernatants from control and LPS-stimulated monocyte incubations were calculated by interpolation from a standard (log/log) curve (0.125-16 ng/ml) fitted by linear regression using a Multicalc software program (Wallac U. K., Ltd.).

1.3. Results

Compounds within the scope of the invention produce 50% inhibition of LPS induced TNF-alpha release from human monocytes at concentrations within the range of 10⁻⁹ M to 10⁻⁴ M, preferably within the range of 10⁻⁹ M to 10⁻⁷ M.

2. Inhibitory Effects of Compounds on Serum TNF-alpha Levels in LPS-challenged Mice

2.1 Treatment of Animals and Measurement of Murine TNF-alpha

Female Balb/c mice (age 6-8 weeks, weight 20-22 g from Charles River, U. K.) in groups of five or more animals were dosed p.o. with compounds (1 to 100 mg/kg) suspended in 1.5% (w/v) carboxymethyl cellulose then challenged after a minimum period of 30 minutes with 30 mg of LPS i.p. After 90 minutes, the animals were killed by carbon dioxide asphyxiation and bled by cardiac puncture. Blood was allowed to clot at 4° C., centrifuged (12,000 g for 5 minutes) and serum taken for TNF-alpha analysis. TNF-alpha levels are measured using a commercially available murine TNF-alpha ELISA kit, purchased from Genzyme (Cat. no. 1509.00), as recommended by the manufacturer. Values for TNF-alpha were calculated from a recombinant murine TNF-alpha standard curve as above.

2.2 Results

Compounds within the scope of the invention inhibit TNF-alpha release in LPS challenged mice up to 50% at doses of 0.1 mg/kg to 100 mg/kg. 

1. A compound of formula (I):

wherein: R¹ is optionally substituted 4-pyridyl; R² is optionally substituted aryl or optionally substituted heteroaryl; R³ represents a group —L¹—R⁷ or —L²—R⁸ where L¹ represents a straight- or branched-chain alkylene linkage containing from 1 to about 6 carbon atoms optionally substituted by halogen or oxo; R⁷ is hydrogen, aryl, cyano, cycloalkyl, heteroaryl, heterocycloalkyl, nitro, —S(O)_(n)R⁹, (where R⁹ is alkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heteroarylalkyl, or heterocycloalkyl and n is zero or an integer 1 or 2), —NHSO₂R⁹, —C(═Z)OR¹⁰ (where Z is an oxygen or sulphur atom and R¹⁰ is hydrogen or R⁹), —C(═Z)R¹⁰, —OR¹⁰, —N(R¹¹)—C(═Z)R⁹ (where R¹¹ is hydrogen or alkyl), —NY¹Y² (where Y¹ and Y² are independently hydrogen, alkenyl, alkyl, alkynyl, aryl, arylalkyl, cycloalkenyl, cycloalkyl, heteroaryl or heteroarylalkyl, or the group —NY¹Y² may form a 5-7 membered cyclic amine which may optionally contain a further heteroatom selected from O, S, or NY³ (where Y³ is hydrogen, alkyl, aryl, arylakyl, —CHO, —C(═Z)R⁹ or —SO₂R⁹), or which may also be fused to additional aryl, heteroaryl, heterocycloalkyl or cycloalkyl rings to form a bicyclic or tricyclic ring system), —SO₂—NY¹Y², —C(═Z)—NY¹Y², —N(R¹¹)—C(═Z)—NY¹Y², —N(OR¹⁰)—C(═Z)—NY¹Y², —N(OR¹⁰)—C(═Z)R¹⁰, —C(═NOR¹⁰)R¹⁰, —C(═Z)NR¹⁰OR¹² (where R¹² is hydrogen, alkyl, aryl or arylalkyl), —N(R¹¹)—C(═NR¹³)—NY¹Y² (where R¹³ is hydrogen, cyano, alkyl, cycloalkyl or aryl), or —N(R¹¹)—C(═Z)OR¹¹; L² represents a direct bond or a straight- or branched-carbon chain comprising from 2 to about 6 carbon atoms and containing a double or triple carbon—carbon bond; and R⁸ is hydrogen, aryl, cycloalkenyl, cycloalkyl, heteroaryl or heterocycloalkyl; R⁴ represents a group —L³—R¹⁴ where L³ represents a direct bond or a straight- or branched-chain alkylene linkage containing from 1 to about 6 carbon atoms (optionally substituted by halogen, hydroxy, alkoxy or oxo); and R¹⁴ is hydrogen, alkyl, azido, hydroxy, alkoxy, aryl, arylalkyloxy, aryloxy, carboxy (or an acid bioisostere), cycloalkyloxy, heteroaryl, heteroarylalkyloxy, heteroaryloxy, heterocycloalkyl, heterocycloalkyloxy, nitro, —NY⁴Y⁵, {where Y⁴ and Y⁵ are independently hydrogen, aryl, cycloalkyl, heterocycloalkyl, heteroaryl or alkyl optionally substituted by alkoxy, aryl, cyano, cycloalkyl, heteroaryl, heterocycloalkyl, hydroxy, oxo, —CO₂R¹⁰, —CONY¹Y² or —NY¹Y₂, or the group —NY⁴Y⁵ may form a 5-7 membered cyclic amine which (i) may be optionally substituted with one or more substituents selected from alkoxy, carboxamido, carboxy, hydroxy, oxo (or a 5, 6, or 7 membered cyclic acetal derivative thereof, R⁹ or alkyl substituted by carboxy, carboxamido or hydroxy (ii) may also contain a further heteroatom selected from O, S, SO₂ or NY⁶ (where Y⁶ is hydrogen, alkyl, aryl, arylalkyl, —C(═Z)R⁹, —C(═Z)OR⁹ or —SO₂R⁹) and (iii) may also be used to additional aryl, heteroaryl, heterocycloalkyl or cycloalkyl rings to form a bicyclic or tricyclic ring system}, —N(R¹⁰)—C(═Z)—R¹⁵ (where R¹⁵ is alkyl, alkoxy, aryl, arylalkyloxy, cycloalkyl, heteroaryl, heteroarylalkoxy or heterocycloalkyl); —N(R¹⁰)—C(═Z)—L⁴—R¹⁶ (where R¹⁶ is alkoxy, aryl, arylalkyloxy, arylalkyloxycarbonylamino, carboxy (or an acid bioisostere), cycloalkyl, cyano, halo, heteroaryl, heteroarylalkoxy, heterocycloalkyl, hydroxy or —NY¹Y², and L⁴ is a straight- or branched-chain alkylene linkage containing from 1 to about 6 carbon atoms), —NH—C(═Z)—NH—R¹⁵, —NH—C(═)—NH—L⁴—R¹⁶, —N(R¹⁰)—SO₂—R¹⁵, —N(R¹⁰)—SO₂—L⁴—R¹⁶, —S(O)_(n)R⁹, —C(═Z)—NY⁴Y⁵ or —C(═Z)—OR⁹; R⁵ represents hydrogen, alkyl or hydroxyalkyl; or R⁴ and R⁵, when attached to the same carbon atom, may form with the said carbon atom a cycloalkyl, cycloalkenyl or heterocycloalkyl ring or a group C═CH₂; R⁶ represents hydrogen or alkyl; and m is zero or an integer 1 or 2; or an N-oxide thereof, or a pharmaceutically acceptable salt or thereof.
 2. A compound according to claim 1 in which R¹ is optionally substituted 4-pyridyl.
 3. A compound according to claim 1 in which R¹ is unsubstituted 4-pyridyl.
 4. A compound according to claim 1 in which R² is optionally substituted phenyl.
 5. A compound according to claim 4 in which R² is phenyl substituted by halogen.
 6. A compound according to claim 4 in which R² is 4-fluorophenyl.
 7. A compound according to claim 1 in which R³ is hydrogen or C₁₋₄alkyl.
 8. A compound according to claim 7 in which R³ is hydrogen.
 9. A compound according to claim 1 in which R⁶ is hydrogen or C₁₋₄alkyl.
 10. A compound according to claim 9 in which R⁶ is hydrogen.
 11. A compound according to claim 1 in which m is an integer
 1. 12. A compound of formula (Ia):

in which R⁴ and R⁵ are as defined in claim 1, or an N-oxide thereof, or a pharmaceutically acceptable or thereof.
 13. A compound according to claim 1 in which R⁴ is a group —L³—R¹⁴ [where L³ is a direct bond and R¹⁴ is selected from alkyl, —NY⁴Y⁵, —N(R¹⁰)—C(═Z)—R¹⁵, —N(R¹⁰)—C(═Z)—L⁴—R¹⁶, —C(═Z)—NY⁴Y⁵ and —C(═Z)OR⁹].
 14. A compound according to claim 1 in which R⁴ is a group —L³—R¹⁴, where L³ is a methylene linkage and R¹⁴ is selected from aryl, heteroaryl, hydroxy, —N(R¹⁰)—C(═Z)—R¹⁵, —N(R¹⁰)—C(═Z)—L⁴—R¹⁶, —NH—C(═Z)—NH—R¹⁵, —NH—C(═Z)—NH—L⁴—R¹⁶, —NY⁴Y⁵ and —N(R¹⁰)—SO₂ —R¹⁵.
 15. A compound according to claim 1 in which R⁵ is hydrogen, C₁₋₄alkyl or hydroxyalkyl.
 16. A compound according to claim 15 in which R⁵ is methyl.
 17. A compound according to claim 15 in which R⁵ is hydroxymethyl.
 18. A compound according to claim 1 in which R⁴ and R⁵ together with the carbon atom to which they are attached represent the group C═CH₂ or a 5-7 membered cyclic ether.
 19. A compound according to claim 1 selected from: {2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol, cis-isomer, (Compound A); {2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanol, trans-isomer, (Compound B); 4-[2-(5,5-dimethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-1H-imidazol-4-yl]-pyridine, (Compound C); C-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-methylamine, cis- and trans-isomers, (Compound D); 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-acetamide, cis- and trans-isomers, (Compound E); 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-acetamide, cis-isomer, (Compound F); 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-acetamide, trans-isomer, (Compound G); 4-[2-(5-azidomethyl-5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-1H-imidazol-4-yl]-pyridine, cis- and trans-isomers, (Compound H); 4-[2-(5-benzyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-1H-imidazol-4-yl]-pyridine, cis- and trans-isomers, (Compound I); 2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid methyl ester, cis- and trans-isomers, (Compound J); 4-[5-(4-fluoro-phenyl)-2-(1,8,10-trioxa-spiro[5.5]undec-9-yl)-1H-imidazol-4-yl]-pyridine, (Compound K); 4-[5-(4-fluoro-phenyl)-2-(1,7,9-trioxa-spiro[4.5]dec-8-yl)-1H-imidazol-4-yl]-pyridine, (Compound L); 4-[2-(5-methyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3-H-imidazol-4-yl]-pyridine, (Compound M); 4-[5-(4-fluoro-phenyl)-2-(5-methylene-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyridine, (Compound N); 4-[2-[1,3]-dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine, (Compound O); 4-[5-(4-fluoro-phenyl)-2-(4-methyl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyridine (R/S)(R/S) isomers, (Compound P); 4-[2-(4,6-dimethyl-[1,3]dioxan-2-yl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine, (R/S)(R/S)(R/S) isomers, (Compound Q); 4-[2-(5-benzyloxy-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine, cis- and trans-isomers, (Compound R); 4-[5-(4-fluoro-phenyl)-2-(5-phenyl-[1,3]dioxan-2-yl)-3H-imidazol-4yl]-pyridine, cis- and trans-isomers, Compound S); 4-[5-(4-fluoro-phenyl)-2-(4-isopropyl-5,5-dimethyl-[1,3]dioxan-2-yl)-3-H-imidazol-4-yl]-pyridine, (R/S)(R/S) isomers, (Compound T); 4-[2-(5,5-diethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine, (Compound U); 4-[2-(2,4-dioxa-spiro[5.5]undec-8-en-3-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine, cis- and trans-isomers, (Compound V); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-benzamide, cis- and trans-isomers, (Compound W); 1-(4-fluoro-phenyl)-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5yl}-thiourea, cis- and trans-isomers, (Compound X); 1-(2,6-dimethyl-phenyl)-3-{2-[4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]-dioxan-5-yl}-thiourea, cis- and trans-isomers, (Compound Y); 4-[5-(4-fluoro-phenyl)-2-(5-methyl-5-pyrrol-1-yl-[1,3]dioxan-2-yl)-3H-imidazol-4-yl]-pyridine, cis- and trans-isomer, (Compound Z); C-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-methylamine, trans-isomer, (Compound AA); C-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-yl]-methylamine, cis-isomer, (Compound AB); 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylmethyl]-acetamide, trans-isomer, (Compound AC); 2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylmethyl]-acetamide, cis-isomer, (Compound AD); 5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine, cis-isomer, (Compound AE); 5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-5-ylamine, trans-isomer, (Compound AF); 5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-4-ylamine, cis- and trans-isomers, (Compound AG); 2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid, trans-isomer, (Compound AH); 2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid, cis-isomer, (Compound AI); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid benzylamid, cis-isomer, (Compound AJ); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid benzylamide, trans-isomer, (Compound AK); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (2-hydroxy-ethyl)-amide, trans-isomer, (Compound AL); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (2-methoxy-ethyl)-amide, trans-isomer, (Compound AM); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid amide, trans-isomer, (Compound AN); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (pyridin-2-ylmethyl)-amide, trans-isomer, (Compound AO); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (pyridin-3-ylmethyl)-amide, trans-isomer, (Compound AP); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (pyridin-4-ylmethyl)-amide, trans-isomer, (Compound AQ); {2-[4-(4-fluoro-phenyl)-5-pyridin-4yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone, trans-isomer, Compound AR); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (3-dimethylamino-propyl)-amide, trans-isomer, (Compound AS); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]-dioxane-5-carboxylic acid [2-(1H-indol-3-yl)-ethyl]-amidek, trans-isomer, (Compound AT); 2-[4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (3-hydroxy-propyl)-amide, trans-isomer, (Compound AU); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (tetrahydro-furan-2-ylmethyl)-amide, trans-isomer, (Compound AV); p1 {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, trans-isomer, (Compound AW); {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-pyrrolidin-1-yl-methanone, trans-isomer, (Compound AX); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2yl]-5-methyl-[1,3]dioxane-5-carboxylic acid butylamide, trans-isomer, (Compound AY); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid dipropylamide, trans-isomer, (Compound AZ); 2-[4(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (3-methoxy-propyl)-amide, trans-isomer, (Compound BA); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid phenethyl-amide, trans-isomer, (Compound BB); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (2-pyridin-2-yl-ethyl)-amide, trans-isomer, (Compound BC); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (furan-2-ylmethyl)-amide, trans-isomer, (Compound BD); {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, trans-isomer, (Compound BE); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid dimethylamide, trans-isomer, (Compound BF); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid propylamide, trans-isomer, (Compound BG); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid cyclopropylamide, trans-isomer, (Compound BH); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid cyclopentylamide, trans-isomer, Compound BI); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid cyclohexylamide, trans-isomer, (Compound BJ); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (2-methoxy-ethyl)-amide, cis-isomer, (Compound BK); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (2-hydroxy-ethyl)-amide, cis-isomer, (Compound BL); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid amide, cis-isomer, (Compound BM); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (pyridin-2-ylmethyl)-amide, cis-isomer, (Compound BN); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dixoane-5-carboxylic acid (pyridin-3-ylmethyl)-amide, cis-isomer, (Compound BO); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (pyridin-4-ylmethyl)-amide, cis-isomer, (Compound BP); {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, cis-isomer, (Compound BQ); {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methyl-piperazin-1-yl)-methanone, cis-isomer, (Compound BR); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (3-dimethylamino-propyl)-amide, cis-isomer, (Compound BS); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid [2-(1H-indol-3-yl)-ethyl]-amide, cis-isomer, (Compound BT); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (3-hydroxy-propyl)-amide, cis-isomer, (Compound BU); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid phenethyl-amide, cis-isomer, (Compound BV); 2-[4-(4-fluoro-phenyl)-5-pyridin-4yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (3-methoxy-propyl)-amide, cis-isomer, (Compound BW); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (2-pyridin-2-yl-ethyl)-amide, cis-isomer, (Compound BX); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (furan-2-ylmethyl)-amide, cis-isomer, (Compound BY); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (tetrahydro-furan-2-ylmethyl)-amide, cis-isomer, (Compound BZ); {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-pyrrolidin-1-yl-methanone, cis-isomer, (Compound CA); {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-piperidin-1yl-methanone, cis-isomer, (Compound CB); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid propylamide, cis-isomer, (Compound CC); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid butylamide, cis-isomer, (Compound CD); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid cyclopropylamide, cis-isomer, (Compound CE); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid cyclopentylamide, cis-isomer, (Compound CF); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid cyclohexylamide, cis-isomer, (Compound CG); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid methylamide, cis-isomer, (Compound CH); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (2-dimethylamino-ethyl)-amide, cis-isomer, (Compound CI); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dixoane-5-carboxylic acid dimethylamide, cis-isomer, (Compound CJ); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid dipropylamide, cis-isomer, (Compound CK); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid ethylamide, cis-isomer, (Compound CL); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid methylamide, trans-isomer, (Compound CM); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid (2-dimethylamino-ethyl)-amide, trans-isomer, (Compound CN); 2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carboxylic acid ethylamide, trans-isomer, (Compound CO); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-3-phenyl-urea, cis-isomer, (Compound CP); 1-ethyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-urea, cis-isomer, (Compound CQ); 1-(3,5-dimethyl-isoxazol-4-yl)-3-{-2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl}-5-methyl-[1,3]dioxan-5-yl]-urea, cis-isomer, (Compound CR); 1-benzyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-urea, cis-isomer, (Compound CS); 1-{2-[4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-3-(2-thiophen-2-yl-ethyl)-urea, cis-isomer, (Compound CT); 1-(3-acetyl-phenyl)-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-urea, cis-isomer, (Compound CU); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-3-phenyl-urea, trans-isomer, (Compound CV); 3-(3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-ureido)-benzoic acid, trans-isomer, (Compound CW); 1-benzyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-urea, trans-isomer, (Compound CX); 1-ethyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-urea, trans-isomer, (Compound CY); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-3-(2-thiophen-2-yl-ethyl)-urea, trans-isomer, (Compound CZ); 1-benzyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-urea, cis-isomer, (Compound DA); 1-ethyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-urea, cis-isomer, (Compound DB); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-phenyl-urea, cis-isomer, (Compound DC); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-phenyl-urea, trans-isomer, (Compound DD); 1-benzyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-urea, trans-isomer, (Compound DE); 1-ethyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-urea, trans-isomer, (Compound DF); 1-{2-[4(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-3-(2-morpholin-4-yl-ethyl)-thiourea, cis-isomer, (Compound DG); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-3-furan-3-ylmethyl-thiourea, cis-isomer, (Compound DH); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-3-pyridin-3-yl-thiourea, cis-isomer, (Compound DI); 1-benzo[1,3]dioxol-5-yl-3-{2-[2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-thiourea, cis-isomer, (Compound DJ); 1-benzo[1,3]dioxol-5-ylmethyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-thiourea, cis-isomer, (Compound DK); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-pyridin-3-yl-thiourea, trans-isomer, (Compound DL); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-(2-morpholin-4-yl-ethyl)-thiourea, trans-isomer, (Compound DM); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-furan-2-ylmethyl-thiourea, trans-isomer, (Compound DN); 1-benzo[1,3]dioxol-5-ylmethyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-thiourea, trans-isomer, (Compound DO); 1-benzo[1,3]dioxol-5-yl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl]-thiourea, cis-isomer, (Compound DP); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-furan-2-ylmethyl-thiourea, cis-isomer, (Compound DQ); 3-(3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-thioureido)-benzoic acid, cis-isomer, (Compound DR); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-pyridin-3-yl-thiourea, cis-isomer, (Compound DS); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-3-(2-morpholin-4-yl-ethyl)-thiourea, cis-isomer, (Compound DT); 1-[1,3]dioxol-5-ylmethyl-3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-thiourea, cis-isomer, (Compound DU); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide, cis-isomer, (Compound DV); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5yl-}-2-phenyl-acetamide, cis-isomer, (Compound DW); cyclohexanecarboxylic acid {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5yl}-amide, cis-isomer, (Compound DX); 2-benzyloxy-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide, trans-isomer, (Compound DY); 2-benzyloxy-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide, cis-isomer, (Compound DZ); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl[1,3]dioxan-5-yl}-acetamide, trans-isomer, (Compound EA); N-[2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-2-phenyl-acetamide, trans-isomer, (Compound EB); cyclohexanecarboxylic acid {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl[1,3]dioxan-5-yl]-amide, trans-isomer, (Compound EC); N-[2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-2-phenyl-acetamide, cis-isomer, (Compound ED); 2-benzyloxy-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide, cis-isomer, (Compound EE); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide, cis-isomer, (Compound EF); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide, cis-isomer, (Compound EG); N-{2-[4-(4-fluoro-phenyl-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide, cis-isomer, (Compound EH); cyclohexanecarboxylic acid {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-amide, cis-isomer, (Compound EI); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-acetamide, trans-isomer, (Compound EJ); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide, trans-isomer, (Compound EK); cyclohexanecarboxylic acid {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]-dioxan-5-ylmethyl}-amide, trans-isomer, (Compound EL); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide, trans-isomer, (Compound EM); 4-{2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-butyric acid, cis-isomer, (Compound EN); 4-({2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-carbamoyl)-butyric acid, cis-isomer (Compound EO); 4-{2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazal-2-yl]-5-methyl-8 1,3]dioxan-5-ylcarbamoyl}-propionic acid, cis-isomer, Compound EF); 4({2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-carbamoyl)-propionic acid, cis-isomer, (Compound EQ); 4({2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-carbamoyl-propionic acid, trans-isomer, (Compound ER); N-{2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanesulphonamide, cis-isomer, (Compound ES); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulphonamide, cis-isomer, (Compound ET); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzenesulphonamide, cis-isomer, (Compound EU); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-C-phenyl-methanesulphonamide, cis-isomer, (Compound EV); thiophene-2-sulphonic acid {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-amide, cis-isomer, (Compound FW); 3,5-dimethyl-isoxazole-4-sulphonic acid {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-amide, cis-isomer, (Compound FX); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-methanesulphonamide, trans-isomer, (Compound EY); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-benzenesulphonamide, trans-isomer, (Compound EZ); thiophene-2-sulphonic acid {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-amide, trans-isomer, (Compound FA); 3,5-dimethyl-isoxazole-4-sulphonic acid {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl[1,3]dioxan-5-ylmethyl}-amide, trans-isomer, (Compound FB); 3-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-propionamide, trans-isomer, (Compound FC); 3-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-propionamide, cis-isomer, (Compound FD); 4-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-butyramide, trans-isomer, (Compound FE); 4-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl[1,3]dioxan-5-yl}-butyramide, cis-isomer, (Compound FF); 2-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide, trans-isomer, (Compound FG); 2-amino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-acetamide, cis-isomer, (Compound FH); 3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-ethyl)-carbamic acid benzyl ester, trans-isomer, (Compound FI); (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-ethyl)-carbamic acid benzyl ester, cis-isomer, Compound FJ); (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-propyl)-carbamic acid benzyl ester, trans-isomer, (Compound FK); (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-ylmethyl-[1,3]dioxan-5-ylcarbamoyl}-propyl)-carbamic acid benzyl ester, cis-isomer, (Compound FL); (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-methyl)-carbamic acid benzyl ester, trans-isomer, (Compound FM); (3-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylcarbamoyl}-methyl)-carbamic acid benzyl ester, cis-isomer, (Compound FN); 4-dimethylamino-N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-butyramide, cis- and trans-isomers, (Compound OF); N-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-benzamide, trans-isomer, (Compound FR); {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-hydroxy-piperidin-1-yl)-methanone, trans isomer, (Compound FS); (1,4-dioxa-8-aza-spiro[4,5]dec-8-yl)-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanone, trans isomer, (Compound FT); 1-{2-[4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carbonyl}-piperidine-4-carboxylic acid ethyl ester, trans isomer, (Compound FU); 1-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxane-5-carbonyl}-piperidine-4-carboxylic acid, trans isomer, (Compound FV); {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-thiomorpholin-4-yl methanone, trans isomer, (Compound FW); (1,1-dioxothiomorpholin-4-yl)-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanone, transisomer, (Compound FX); {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxymethyl-piperidin-1-yl)-methanone, trans isomer, (Compound FY); {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-piperidin-1-yl)-methanone, trans isomer, (Compound FZ); (2,6-dimethyl-morpholin-4-yl)-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-methanone, trans isomer, (Compound GA); {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone, trans isomer, (Compound GB); {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-(4-methoxy-piperidin-1-yl)-methanone, trans isomer, (Compound GC); {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-[4-(2-hydroxy-ethyl)-piperidin-1-yl]-methanone, trans isomer, (Compound GD); {5-Amino-2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol, cis isomer, (Compound LE); {5-Amino-2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-[1,3]dioxan-5-yl}-methanol, trans isomer, (Compound LF); {2-[4-(4-Fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-nitro-[1,3]dioxan-5-yl}-methanol, cis isomer, (Compound LG); {2-[4-(4-Fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-nitro-[1,3]dioxan-5-yl}-methanol, trans isomer, (Compound LH); C-{2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5,5-dimethyl-[1,3]dioxan-4-yl}-methylamine (Compound LI); 4-[2-(5,5-dimethyl-4-nitromethyl-[1,3]dioxan-2-yl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyridine (Compound LJ); or the corresponding N-oxide; or a pharmaceutically acceptable salt or thereof.
 20. {2-[4-(4-Fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, trans-isomer, (Compound AW); or the corresponding N-oxide or a pharmaceutically acceptable salt or solvate thereof.
 21. The mesylate salt of {2-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl[1,3]dioxan-5-yl}-morpholin-4-yl-methanone, trans-isomer.
 22. A pharmaceutical composition comprising a compound according to claim 1 together with a pharmaceutically acceptable carrier or excipient.
 23. A method for the treatment of asthma in a patient in need thereof, comprising administering to said patient a pharmaceutically effective amount of a compound according to claim
 1. 24. A method for the treatment of joint inflammation in a patient in need thereof, comprising administering to said patient a pharmaceutically effective amount of a compound according to claim
 1. 25. A compound of formula (II)

wherein R¹ represents optionally substituted 4-pyridyl, R² optionally substituted aryl or optionally substituted heteroaryl, R¹⁹ is hydrogen or a protecting group and R²⁰ is —CHO or —CH(OMe)₂.
 26. Process for the preparation of a compound of formula (I), wherein R¹, R², R⁴, R⁵, R⁶ and m are as defined in claim 1 and R³ is hydrogen, comprising reacting a compound of formula (II)

wherein R¹ and R² are as defined in claim 1, R¹⁹ is hydrogen or a protecting group and R²⁰ is —CHO or —CH(OMe)₂, with a compound of formula (III)

wherein R⁴, R⁵, R⁶ and m are as defined in Claim 1, under acidic conditions.
 27. Process for the preparation of a compound formula (II)

wherein R¹ and R² are as defined in claim 1, R¹⁹ is hydrogen and R²⁰ is —CH(OMe)₂, this process comprising reacting a compound of formula (2)

wherein R¹ and R² are as defined in claim 1, with glyoxal 1,1-dimethylacetal and ammonium acetate. 